Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1986 Aug 1;164(2):407–427. doi: 10.1084/jem.164.2.407

Variable region sequences of murine IgM anti-IgG monoclonal autoantibodies (rheumatoid factors). A structural explanation for the high frequency of IgM anti-IgG B cells

PMCID: PMC2188225  PMID: 3088205

Abstract

The nucleotide sequences of heavy and light chains from 10 monoclonal IgM anti-IgG1 (RF) antibodies were determined and reported here as translated amino acid sequences. Only three families of VK light chains were used in these antibodies: VK1 (two examples), VK8 (three examples), and VK19 (four examples). This represents a significant nonrandom selection of light chains. In contrast, all other variable region gene segments (i.e., VH, DH, JH, and JK) were used in a pattern consistent with random selection from the available pool of germline genes. In two cases, the same anti-IgG1 specificity was generated by a combination of very homologous light chains with unrelated heavy chains. We infer from this that the light chain is the segment used by these antibodies to bind IgG1. The nature of these sequences provides an explanation for the curious observation that as many as 15% of splenic B cells in normal mice may be expressing IgM anti-IgG; if, as our data suggest, certain light chains in combination with many different heavy chains can be used in assembling the anti-IgG specificity, then, because of combinatorial association in which the heavy chain is not relevant for specificity, the fraction of IgM- producing B cells expressing these light chains should approximate the fraction of B cells making IgM anti-IgG. We calculate, based on data presented in several other studies, that 5-17% of B cells express one of the VK types observed in monoclonal RF. This agrees well with estimates for the number of B cells making IgM anti-IgG. In addition, our findings could rule out other explanations of the high percentage of B cells making RF, such as constant stimulation by antigen or presence of numerous antigenic epitopes since it was shown that IgM anti-IgG1 antibodies are not somatically mutated and that they are structurally homogeneous. We aligned the VK sequences of the RF in hopes of finding some primary sequence homology between the represented VK families which might point to residues involved in the binding interaction. Although we found no such homology in the hypervariable regions, we did find significant and unexpected homology in the FR2 and FR3 of these light chains. We noted that these regions are exposed in the Ig structure and postulate that they may be involved in a unique type of binding interaction between two Ig family domains, i.e., VK binding to a constant region domain of IgG.

Full Text

The Full Text of this article is available as a PDF (1.4 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ABRUZZO J. L., CHRISTIAN C. L. The induction of a rheumatoid factor-like substance in rabbits. J Exp Med. 1961 Nov 1;114:791–806. doi: 10.1084/jem.114.5.791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Acuto O., Hussey R. E., Reinherz E. L. Multiple class I and class II major histocompatibility complex allospecificities are generated with T cell receptor variable (V) domains created by a single Ti beta V gene family. J Exp Med. 1985 Oct 1;162(4):1387–1392. doi: 10.1084/jem.162.4.1387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Agnello V., Arbetter A., Ibanez de Kasep G., Powell R., Tan E. M., Joslin F. Evidence for a subset of rheumatoid factors that cross-react with DNA-histone and have a distinct cross-idiotype. J Exp Med. 1980 Jun 1;151(6):1514–1527. doi: 10.1084/jem.151.6.1514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Alt F. W., Baltimore D. Joining of immunoglobulin heavy chain gene segments: implications from a chromosome with evidence of three D-JH fusions. Proc Natl Acad Sci U S A. 1982 Jul;79(13):4118–4122. doi: 10.1073/pnas.79.13.4118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Andersson J., Coutinho A., Melchers F. Frequencies of mitogen-reactive B cells in the mouse. II. Frequencies of B cells producing antibodies which lyse sheep or horse erythrocytes, and trinitrophenylated or nitroiodophenylated sheep erythrocytes. J Exp Med. 1977 Jun 1;145(6):1520–1530. doi: 10.1084/jem.145.6.1520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Augustin A. A., Coutinho A. Specific T helper cells that activate B cells polyclonally. In vitro enrichment and cooperative function. J Exp Med. 1980 Mar 1;151(3):587–601. doi: 10.1084/jem.151.3.587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Basta P., Kubagawa H., Kearney J. F., Briles D. E. Ten percent of normal B cells and plasma cells share A VH determinant(s) (J606-GAC) with a distinct subset of murine VHIII plasmacytomas. J Immunol. 1983 May;130(5):2423–2428. [PubMed] [Google Scholar]
  8. Berek C., Griffiths G. M., Milstein C. Molecular events during maturation of the immune response to oxazolone. Nature. 1985 Aug 1;316(6027):412–418. doi: 10.1038/316412a0. [DOI] [PubMed] [Google Scholar]
  9. Bernabé R. R., Coutinho A., Martinez-A C., Cazenave P. A. Immune networks. Frequencies of antibody- and idiotype-producing B cell clones in various steady states. J Exp Med. 1981 Aug 1;154(2):552–556. doi: 10.1084/jem.154.2.552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Biggin M. D., Gibson T. J., Hong G. F. Buffer gradient gels and 35S label as an aid to rapid DNA sequence determination. Proc Natl Acad Sci U S A. 1983 Jul;80(13):3963–3965. doi: 10.1073/pnas.80.13.3963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Bona C. A., Finley S., Waters S., Kunkel H. G. Anti-immunoglobulin antibodies. III. Properties of sequential anti-idiotypic antibodies to heterologous anti-gamma globulins. Detection of reactivity of anti-idiotype antibodies with epitopes of Fc fragments (homobodies) and with epitopes and idiotopes (epibodies). J Exp Med. 1982 Oct 1;156(4):986–999. doi: 10.1084/jem.156.4.986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Bona C. A., Goldberg B., Metzger D., Urbain J., Kunkel H. G. Anti-immunoglobulin antibodies IV. Cross-reaction of anti-idiotypic antibodies specific for rabbit and murine anti-a1 allotype antibodies with Fc fragment of human immunoglobulins. Eur J Immunol. 1984 Jun;14(6):548–552. doi: 10.1002/eji.1830140612. [DOI] [PubMed] [Google Scholar]
  13. Brodeur P. H., Riblet R. The immunoglobulin heavy chain variable region (Igh-V) locus in the mouse. I. One hundred Igh-V genes comprise seven families of homologous genes. Eur J Immunol. 1984 Oct;14(10):922–930. doi: 10.1002/eji.1830141012. [DOI] [PubMed] [Google Scholar]
  14. Capra J. D., Kehoe J. M. Structure of antibodies with shared idiotypy: the complete sequence of the heavy chain variable regions of two immunoglobulin M anti-gamma globulins. Proc Natl Acad Sci U S A. 1974 Oct;71(10):4032–4036. doi: 10.1073/pnas.71.10.4032. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Chen P. P., Goñi F., Fong S., Jirik F., Vaughan J. H., Frangione B., Carson D. A. The majority of human monoclonal IgM rheumatoid factors express a "primary structure-dependent" cross-reactive idiotype. J Immunol. 1985 May;134(5):3281–3285. [PubMed] [Google Scholar]
  16. Chen P. P., Gõni F., Houghten R. A., Fong S., Goldfien R., Vaughan J. H., Frangione B., Carson D. A. Characterization of human rheumatoid factors with seven antiidiotypes induced by synthetic hypervariable region peptides. J Exp Med. 1985 Aug 1;162(2):487–500. doi: 10.1084/jem.162.2.487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  18. Clarke S. H., Huppi K., Ruezinsky D., Staudt L., Gerhard W., Weigert M. Inter- and intraclonal diversity in the antibody response to influenza hemagglutinin. J Exp Med. 1985 Apr 1;161(4):687–704. doi: 10.1084/jem.161.4.687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Clarkson A. B., Jr, Mellow G. H. Rheumatoid factor-like immunoglobulin M protects previously uninfected rat pups and dams from Trypanosoma lewisi. Science. 1981 Oct 9;214(4517):186–188. doi: 10.1126/science.7025211. [DOI] [PubMed] [Google Scholar]
  20. Cory S., Tyler B. M., Adams J. M. Sets of immunoglobulin V kappa genes homologous to ten cloned V kappa sequences: implications for the number of germline V kappa genes. J Mol Appl Genet. 1981;1(2):103–116. [PubMed] [Google Scholar]
  21. Coulie P. G., Van Snick J. Rheumatoid factor (RF) production during anamnestic immune responses in the mouse. III. Activation of RF precursor cells is induced by their interaction with immune complexes and carrier-specific helper T cells. J Exp Med. 1985 Jan 1;161(1):88–97. doi: 10.1084/jem.161.1.88. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Coulie P., Van Snick J. Rheumatoid factors and secondary immune responses in the mouse. II. Incidence, kinetics and induction mechanisms. Eur J Immunol. 1983 Nov;13(11):895–899. doi: 10.1002/eji.1830131107. [DOI] [PubMed] [Google Scholar]
  23. Crews S., Griffin J., Huang H., Calame K., Hood L. A single VH gene segment encodes the immune response to phosphorylcholine: somatic mutation is correlated with the class of the antibody. Cell. 1981 Jul;25(1):59–66. doi: 10.1016/0092-8674(81)90231-2. [DOI] [PubMed] [Google Scholar]
  24. Darsley M. J., Rees A. R. Nucleotide sequences of five anti-lysozyme monoclonal antibodies. EMBO J. 1985 Feb;4(2):393–398. doi: 10.1002/j.1460-2075.1985.tb03641.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Devaux C., Moinier D., Mazza G., Guo X. J., Marchetto S., Fougereau M., Pierres M. Preferential expression of VK21E light chains on IdX Ia.7 positive monoclonal anti-I-E antibodies. J Immunol. 1985 Jun;134(6):4024–4030. [PubMed] [Google Scholar]
  26. Dresser D. W. Most IgM-producing cells in the mouse secrete auto-antibodies (rheumatoid factor). Nature. 1978 Aug 3;274(5670):480–483. doi: 10.1038/274480a0. [DOI] [PubMed] [Google Scholar]
  27. Eisenberg R. The specificity and polyvalency of binding of a monoclonal rheumatoid factor. Immunochemistry. 1976 Apr;13(4):355–359. doi: 10.1016/0019-2791(76)90347-5. [DOI] [PubMed] [Google Scholar]
  28. Gibson D. M. Evidence for 65 electrophoretically distinct groups of light chains in BALB/c and NZB myelomas. Mol Immunol. 1984 May;21(5):421–432. doi: 10.1016/0161-5890(84)90040-3. [DOI] [PubMed] [Google Scholar]
  29. Hawley R. G., Shulman M. J., Murialdo H., Gibson D. M., Hozumi N. Mutant immunoglobulin genes have repetitive DNA elements inserted into their intervening sequences. Proc Natl Acad Sci U S A. 1982 Dec;79(23):7425–7429. doi: 10.1073/pnas.79.23.7425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Heber-Katz E., Schwartz R. H., Matis L. A., Hannum C., Fairwell T., Appella E., Hansburg D. Contribution of antigen-presenting cell major histocompatibility complex gene products to the specificity of antigen-induced T cell activation. J Exp Med. 1982 Apr 1;155(4):1086–1099. doi: 10.1084/jem.155.4.1086. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Izui S., Eisenberg R. A., Dixon F. J. IgM rheumatoid factors in mice injected with bacterial lipopolysaccharides. J Immunol. 1979 May;122(5):2096–2102. [PubMed] [Google Scholar]
  32. Joho R., Gershenfeld H., Weissman I. L. Evolution of a multigene family of V kappa germ line genes. EMBO J. 1984 Jan;3(1):185–191. doi: 10.1002/j.1460-2075.1984.tb01782.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Julius M. A., McKean D. J., Potter M., Feldmann R. J., Weigert M. The structural basis of antigenic determinants on V kappa 21 light chains. Mol Immunol. 1981 Jan;18(1):1–9. doi: 10.1016/0161-5890(81)90042-0. [DOI] [PubMed] [Google Scholar]
  34. Julius M. A., McKean D. J., Potter M., Weigert M. Expression of kappa chains of the V kappa 21 group in Mus musculus and related species. Mol Immunol. 1981 Jan;18(1):11–17. doi: 10.1016/0161-5890(81)90043-2. [DOI] [PubMed] [Google Scholar]
  35. Kaartinen M., Griffiths G. M., Markham A. F., Milstein C. mRNA sequences define an unusually restricted IgG response to 2-phenyloxazolone and its early diversification. 1983 Jul 28-Aug 3Nature. 304(5924):320–324. doi: 10.1038/304320a0. [DOI] [PubMed] [Google Scholar]
  36. Kunkel H. G., Agnello V., Joslin F. G., Winchester R. J., Capra J. D. Cross-idiotypic specificity among monoclonal IgM proteins with anti- -globulin activity. J Exp Med. 1973 Feb 1;137(2):331–342. doi: 10.1084/jem.137.2.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Kurosawa Y., Tonegawa S. Organization, structure, and assembly of immunoglobulin heavy chain diversity DNA segments. J Exp Med. 1982 Jan 1;155(1):201–218. doi: 10.1084/jem.155.1.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. LeJeune J. M., Briles D. E., Lawton A. R., Kearney J. F. Estimate of the light chain repertoire size of fetal and adult BALB/cJ and CBA/J mice. J Immunol. 1982 Aug;129(2):673–677. [PubMed] [Google Scholar]
  39. Loh D. Y., Bothwell A. L., White-Scharf M. E., Imanishi-Kari T., Baltimore D. Molecular basis of a mouse strain-specific anti-hapten response. Cell. 1983 May;33(1):85–93. doi: 10.1016/0092-8674(83)90337-9. [DOI] [PubMed] [Google Scholar]
  40. Lévy M. Frequencies of phosphorylcholine-specific and T15-associated 10/13 idiotope-positive B cells within lipopolysaccharide-reactive B cells of adult BALB/c mice. Eur J Immunol. 1984 Sep;14(9):864–868. doi: 10.1002/eji.1830140917. [DOI] [PubMed] [Google Scholar]
  41. Manser T., Huang S. Y., Gefter M. L. Influence of clonal selection on the expression of immunoglobulin variable region genes. Science. 1984 Dec 14;226(4680):1283–1288. doi: 10.1126/science.6334361. [DOI] [PubMed] [Google Scholar]
  42. Moynet D., MacLean S. J., Ng K. H., Anctil D., Gibson D. M. Polymorphism of kappa variable region (V kappa-1) genes in inbred mice: relationship to the Ig kappa-Ef2 serum light chain marker. J Immunol. 1985 May;134(5):3455–3460. [PubMed] [Google Scholar]
  43. Near R. I., Manser T., Gefter M. L. The generation of major and minor idiotype-bearing families of anti-p-azophenylarsonate antibodies; stochastic utilization of VH gene segments. J Immunol. 1985 Mar;134(3):2004–2009. [PubMed] [Google Scholar]
  44. Nemazee D. A. Immune complexes can trigger specific, T cell-dependent, autoanti-IgG antibody production in mice. J Exp Med. 1985 Jan 1;161(1):242–256. doi: 10.1084/jem.161.1.242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Nemazee D. A., Sato V. L. Induction of rheumatoid antibodies in the mouse. Regulated production of autoantibody in the secondary humoral response. J Exp Med. 1983 Aug 1;158(2):529–545. doi: 10.1084/jem.158.2.529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Perlmutter R. M., Kearney J. F., Chang S. P., Hood L. E. Developmentally controlled expression of immunoglobulin VH genes. Science. 1985 Mar 29;227(4694):1597–1601. doi: 10.1126/science.3975629. [DOI] [PubMed] [Google Scholar]
  47. Perlmutter R. M., Klotz J. L., Bond M. W., Nahm M., Davie J. M., Hood L. Multiple VH gene segments encode murine antistreptococcal antibodies. J Exp Med. 1984 Jan 1;159(1):179–192. doi: 10.1084/jem.159.1.179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Peterson P. A., Cunningham B. A., Berggård I., Edelman G. M. 2 -Microglobulin--a free immunoglobulin domain. Proc Natl Acad Sci U S A. 1972 Jul;69(7):1697–1701. doi: 10.1073/pnas.69.7.1697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Pons-Estel B., Goñi F., Solomon A., Frangione B. Sequence similarities among kappa IIIb chains of monoclonal human IgM kappa autoantibodies. J Exp Med. 1984 Sep 1;160(3):893–904. doi: 10.1084/jem.160.3.893. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Potter M., Newell J. B., Rudikoff S., Haber E. Classification of mouse VK groups based on the partial amino acid sequence to the first invariant tryptophan: impact of 14 new sequences from IgG myeloma proteins. Mol Immunol. 1982 Dec;19(12):1619–1630. doi: 10.1016/0161-5890(82)90273-5. [DOI] [PubMed] [Google Scholar]
  51. Primi D., Mami F., Le Guern C., Cazenave P. A. Mitogen-reactive B cell subpopulations selectively express different sets of V regions. J Exp Med. 1982 Jul 1;156(1):181–190. doi: 10.1084/jem.156.1.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Reth M., Hämmerling G. J., Rajewsky K. Analysis of the repertoire of anti-NP antibodies in C57BL/6 mice by cell fusion. I. Characterization of antibody families in the primary and hyperimmune response. Eur J Immunol. 1978 Jun;8(6):393–400. doi: 10.1002/eji.1830080605. [DOI] [PubMed] [Google Scholar]
  53. Rubin C. M., Schmid C. W. Pyrimidine-specific chemical reactions useful for DNA sequencing. Nucleic Acids Res. 1980 Oct 24;8(20):4613–4619. doi: 10.1093/nar/8.20.4613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Rubin R. L., Balderas R. S., Tan E. M., Dixon F. J., Theofilopoulos A. N. Multiple autoantigen binding capabilities of mouse monoclonal antibodies selected for rheumatoid factor activity. J Exp Med. 1984 May 1;159(5):1429–1440. doi: 10.1084/jem.159.5.1429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Rudikoff S., Pawlita M., Pumphrey J., Mushinski E., Potter M. Galactan-binding antibodies. Diversity and structure of idiotypes. J Exp Med. 1983 Nov 1;158(5):1385–1400. doi: 10.1084/jem.158.5.1385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Rupp F., Acha-Orbea H., Hengartner H., Zinkernagel R., Joho R. Identical V beta T-cell receptor genes used in alloreactive cytotoxic and antigen plus I-A specific helper T cells. 1985 May 30-Jun 5Nature. 315(6018):425–427. doi: 10.1038/315425a0. [DOI] [PubMed] [Google Scholar]
  57. Sablitzky F., Wildner G., Rajewsky K. Somatic mutation and clonal expansion of B cells in an antigen-driven immune response. EMBO J. 1985 Feb;4(2):345–350. doi: 10.1002/j.1460-2075.1985.tb03635.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Segal D. M., Padlan E. A., Cohen G. H., Rudikoff S., Potter M., Davies D. R. The three-dimensional structure of a phosphorylcholine-binding mouse immunoglobulin Fab and the nature of the antigen binding site. Proc Natl Acad Sci U S A. 1974 Nov;71(11):4298–4302. doi: 10.1073/pnas.71.11.4298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Smith G. P. Sequence of the full-length immunoglobulin kappa-chain of mouse myeloma MPC 11. Biochem J. 1978 May 1;171(2):337–347. doi: 10.1042/bj1710337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Stassin V., Coulie P. G., Birshtein B. K., Secher D. S., Van Snick J. Determinants recognized by murine rheumatoid factors: molecular localization using a panel of mouse myeloma variant immunoglobulins. J Exp Med. 1983 Nov 1;158(5):1763–1768. doi: 10.1084/jem.158.5.1763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Tonnelle C., Rocca-Serra J., Moulin A., Moinier D., Fougereau M. V kappa gene family in (Glu60 Ala30 Tyr10)n (GAT)-specific antibodies that express CGAT (or pGAT) public idiotypic specificities. Protein and mRNA sequencing of eight monoclonal V kappa chains. J Exp Med. 1983 Nov 1;158(5):1415–1427. doi: 10.1084/jem.158.5.1415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Van Snick J. L., Coulie P. Monoclonal anti-IgG autoantibodies derived from lipopolysaccharide-activated spleen cells of 129/Sv mice. J Exp Med. 1982 Jan 1;155(1):219–230. doi: 10.1084/jem.155.1.219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Van Snick J., Coulie P. Rheumatoid factors and secondary immune responses in the mouse. I. Frequent occurrence of hybridomas secreting IgM anti-IgG1 autoantibodies after immunization with protein antigens. Eur J Immunol. 1983 Nov;13(11):890–894. doi: 10.1002/eji.1830131106. [DOI] [PubMed] [Google Scholar]
  64. Weigert M., Riblet R. Genetic control of antibody variable regions. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 2):837–846. doi: 10.1101/sqb.1977.041.01.093. [DOI] [PubMed] [Google Scholar]
  65. Welch M. J., Fong S., Vaughan J., Carson D. Increased frequency of rheumatoid factor precursor B lymphocytes after immunization of normal adults with tetanus toxoid. Clin Exp Immunol. 1983 Feb;51(2):299–304. [PMC free article] [PubMed] [Google Scholar]
  66. Wood D. L., Coleclough C. Different joining region J elements of the murine kappa immunoglobulin light chain locus are used at markedly different frequencies. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4756–4760. doi: 10.1073/pnas.81.15.4756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Wysocki L. J., Margolies M. N., Huang B., Nemazee D. A., Wechsler D. S., Sato V. L., Smith J. A., Gefter M. L. Combinational diversity within variable regions bearing the predominant anti-p-azophenylarsonate idiotype of strain A mice. J Immunol. 1985 Apr;134(4):2740–2747. [PubMed] [Google Scholar]
  68. Yagüe J., White J., Coleclough C., Kappler J., Palmer E., Marrack P. The T cell receptor: the alpha and beta chains define idiotype, and antigen and MHC specificity. Cell. 1985 Aug;42(1):81–87. doi: 10.1016/s0092-8674(85)80103-3. [DOI] [PubMed] [Google Scholar]
  69. Yancopoulos G. D., Desiderio S. V., Paskind M., Kearney J. F., Baltimore D., Alt F. W. Preferential utilization of the most JH-proximal VH gene segments in pre-B-cell lines. Nature. 1984 Oct 25;311(5988):727–733. doi: 10.1038/311727a0. [DOI] [PubMed] [Google Scholar]
  70. van Snick J. L., Masson P. L. Incidence and specificities of IgA and IgM anti-AgG autoantibodies in various mouse strains and colonies. J Exp Med. 1980 Jan 1;151(1):45–55. doi: 10.1084/jem.151.1.45. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES