Evidence for V(H) Gene Replacement in Human Fetal B Cells

ABSTRACT

BACKGROUND: In contrast to evidences of Ig H chain receptor editing in transformed cell lines and transgenic mouse models, there has been no direct evidence that this phenomenon occurs in human developing B cells. METHODS: V(H)DJ(H) rearrangements were obtained from genomic DNA of individual IgM- B cells from liver and IgM+B cells from bone marrow of 18 wk of gestation human fetus by PCR amplification and direct sequencing. RESULTS: We found three examples of H chain receptor editing from IgM+ and IgM+human fetal B cells. Two types of V(H) replacements were identified. The first involved V(H) hybrid formation, in which part of a V(H) gene from the initial VDJ rearrangement is replaced by part of an upstream V(H) gene at the site of cryptic RSS. The second involved a gene conversion like replacement of CDR2, in which another V(H) gene donated a portion of its CDR2 sequence to the initial VDJ rearrangement. CONCLUSION: These data provide evidence of receptor editing at the H chain loci in developing human B cells, and also the first evidence of a gene conversion event in human Ig genes.