Germline structure and differential utilization of Igh(a) and Igh(b) V(H)10 genes

Ab heavy chains encoded by mouse V(H)10 genes have been of particular inter est due to their frequent association with DNA binding. We reported previou sly that V(H)10 sequences are over-represented in the preimmune repertoire considering the apparent number of germline-encoded V(H)10 gene segments, I n this report, we show that the V(H)10 family consists of three and two ger mline genes in the Igh(a) and Igh(b) haplotypes, respectively. The complete nucleotide sequences of these five genes, including promoters and recombin ation signal sequences, were determined and allow unambiguous assignment of allelic relationships. The usage of individual V(H)10 genes varied signifi cantly and ranged from 0.2% to an extraordinary 7.2% of the V-H genes expre ssed by splenic B cells, Since the promoter and recombination signal sequen ce elements of all five V(H)10 genes are identical, we suggest that the few amino acid differences encoded by these five germline V(H)10 genes determi ne their representation in the preimmune repertoire. Rearrangements of the most frequently used V(H)10 gene have an apparent bias for histidine at pos ition 95 of complementarity-determining region-3 (CDR3). These CDR3s are al so biased for asparagine, an amino acid associated with the CDRs of DNA bin ding Abs, Together, these results suggest that high V(H)10 gene use is the result of B cell receptor-mediated selection and may involve DNA and/or lig ands that share antigenic features with DNA.