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

• Published in: The Journal of immunology (1950) Vol. 165; no. 2; pp. 852 - 859
• Main Authors: Fitzsimmons, S P, Clark, K J, Mostowski, H S, Shapiro, M A
• Format: Journal Article
• Language: English
• Published: United States 15.07.2000
• Subjects: Animals; B-Lymphocytes - cytology; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Bone Marrow Cells - cytology; Bone Marrow Cells - immunology; Bone Marrow Cells - metabolism; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell Separation; Female; Gene Rearrangement, B-Lymphocyte; Genes, Immunoglobulin; Immunoglobulin kappa-Chains - biosynthesis; Immunoglobulin kappa-Chains - genetics; Immunoglobulin Variable Region - biosynthesis; Immunoglobulin Variable Region - genetics; Male; Mice; Mice, Inbred BALB C; Multigene Family - immunology; Recombination, Genetic - immunology; Spleen - cytology; Spleen - immunology; Spleen - metabolism; Transcription, Genetic - immunology
• ISSN: 0022-1767
• DOI: 10.4049/jimmunol.165.2.852

The V kappa10 family of murine light chain Ig genes is composed of three members, two of which (V kappa 10A and V kappa 10B) are well used. V kappa 10C, 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 can recombine, but mRNA levels in spleen were extremely low relative to those of V kappa 10A and V kappa 10B. Furthermore, while the V kappa 10C promoter was efficient in B cells, it was shown to work inefficiently in pre-B cell 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-represented in V kappa cDNA libraries, but that the frequency of its sterile transcripts in pre-B cells surpasses both V kappa 10A and V kappa 10B, indicating that the gene is as accessible as V kappa 10A and V kappa 10B to the recombination 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 nonproductive to productive recombination ratio. As B cells develop, however, both the frequency of V kappa 10C rearrangements and the presence of productive rearrangements decline, indicating that these cells are in some fashion being eliminated.