Underutilization of the V kappa 10C gene in the B cell repertoire is due to the loss of productive VJ rearrangements during B cell development

Citation
Sp. Fitzsimmons et al., Underutilization of the V kappa 10C gene in the B cell repertoire is due to the loss of productive VJ rearrangements during B cell development, J IMMUNOL, 165(2), 2000, pp. 852-859
Citations number
44
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
00221767 → ACNP
Volume
165
Issue
2
Year of publication
2000
Pages
852 - 859
Database
ISI
SICI code
0022-1767(20000715)165:2<852:UOTVK1>2.0.ZU;2-O
Abstract
The V kappa 10 family of murine light chain Ig genes is composed of three m embers, two of which (V kappa 10A and V kappa 10B) are well used. V kappa 1 0C, the third member of this family, is not detected in any expressed Abs, Our previous work showed that V kappa 10C is structurally functional and ca n recombine, but mRNA levels in spleen were extremely low relative to thole of V kappa 10A and V kappa 10B, Furthermore, while the V kappa 10C promote r was efficient in Il cells, it was shown to work inefficiently in pre-B ce ll lines. Here, we extend our analysis of the V kappa 10 family and examine V kappa 10 gene accessibility, their representation in V kappa cDNA phage libraries, and the frequency and nature of rearrangements during different stages of B cell development. We demonstrate that V kappa 10C is under-repr esented in V kappa cDNA libraries, but that the frequency of its sterile tr anscripts in pre-B cells surpasses both V kappa 10A and V kappa 10B, indica ting that the gene is as accessible as V kappa 10A and V kappa 10B to the r ecombination machinery. We also demonstrate that V kappa 10C recombines at a frequency equal to that of V kappa 10A in pre-B cells and has a normal no nproductive to productive recombination ratio. As B cells develop, however, both the frequency of V kappa 10C rearrangements and the presence of produ ctive rearrangements decline, indicating that these cells are in some fashi on being eliminated.