Fig. 6. Mechanism of ordered VH recombination. Pro-B cell subsets as defined by Hardy are shown in the circles. Genomic structures of the Ig loci are shown in bold below each circle (GL = germline). Presumed ongoing rearrangements in each subset are indicated in parentheses below the genomic structure. Recombination at the IgH locus is initiated in late A fraction cells; our observations suggest that only the DH–Cµ part of the locus is accessible to recombinase at this stage, resulting in DH to JH recombination. Proximal VH gene families are activated on DJH recombined alleles as outlined in the text. We propose that distal VH genes, that are activated by IL-7, lag behind the proximal VHs because IL-7 responsiveness is gained gradually during B-cell development based on Wei et al. (2000) (indicated by a triangle). Preferential rearrangement of proximal VH genes is therefore a consequence of the late activation of the 5′ VH genes via the IL-7 receptor.