Germline Structure and Differential Utilization of Igh super(a) and Igh super(b) V sub(H)10 Genes

• Published in: The Journal of immunology (1950) Vol. 162; no. 3; pp. 1541 - 1550
• Main Authors: Whitcomb, E A, Haines, B B, Parmelee, A P, Pearlman, A M, Brodeur, PH
• Format: Journal Article
• Language: English
• Published: 01-02-1999
• ISSN: 0022-1767

Ab heavy chains encoded by mouse V sub(H)10 genes have been of particular interest due to their frequent association with DNA binding. We reported previously that V sub(H)10 sequences are over-represented in the preimmune repertoire considering the apparent number of germline-encoded V sub(H)10 gene segments. In this report, we show that the V sub(H)10 family consists of three and two germline genes in the Igh super(a) and Igh super(b) haplotypes, respectively. The complete nucleotide sequences of these five genes, including promoters and recombination signal sequences, were determined and allow unambiguous assignment of allelic relationships. The usage of individual V sub(H)10 genes varied significantly and ranged from 0.2% to an extraordinary 7.2% of the V sub(H) genes expressed by splenic B cells. Since the promoter and recombination signal sequence elements of all five V sub(H)10 genes are identical, we suggest that the few amino acid differences encoded by these five germline V sub(H)10 genes determine their representation in the preimmune repertoire. Rearrangements of the most frequently used V sub(H)10 gene have an apparent bias for histidine at position 95 of complementarity-determining region-3 (CDR3). These CDR3s are also biased for asparagine, an amino acid associated with the CDRs of DNA binding Abs. Together, these results suggest that high V sub(H)10 gene use is the result of B cell receptor-mediated selection and may involve DNA and/or ligands that share antigenic features with DNA.