Two V_H5 family genes expressed by human peripheral B cells display differential mutational frequencies in the V_H region

The heavy chain variable segment gene (V_H)5 family, one of the seven immunoglobulin (Ig) V_H families, contains two functional genes, VH251 and VH32. To investigate functional differences between these V_H5 family genes, V_H segments expressed by human peripheral B cells were sequenced and analyzed. One hundred fifty-three sequences with unique V_HDJ_H recombinations were obtained from 17 adults. The mutational frequency of VH32 derived sequences (6.4%) was higher than that of VH251 derived sequences (4.4%), resulting in a significant difference (P<0.01). Significant differences in mutational frequencies between VH251 and VH32 derived sequences were observed in CDRs and FRs. No significant differences were found in CDR3 length distribution, D segment usage, or J_H segment usage between VH251 and VH32 derived sequences. These results suggest that mutational frequency is affected, in part, by V_H gene structure. The difference may occur after recombinational events in B cell development.