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.
نویسندگان
چکیده
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.
منابع مشابه
Diversity of T-cell receptor Gene Rearrangements in South Indian Patients with Common Acute Lymphoblastic Leukemia
Background: Precursor B-Acute Lymphoblastic Leukemia (precursor B-ALL) oc-curs due to the uncontrolled proliferation of B-lymphoid precursors arrested at a par-ticular stage of B-cell development. Precursor-B-ALL is classified mainly into pro-B-ALL, common-ALL and pre-B-ALL. The Common Acute Lymphoblastic Antigen CD10 is the marker for common-ALL. Objective: This study was aimed to examine the ...
متن کاملIg lambda and heavy chain gene usage in early untreated systemic lupus erythematosus suggests intensive B cell stimulation.
To determine the distribution of Vlambda and Jlambda as well as VH and JH gene usage in a patient with systemic lupus erythematosus (SLE), productive and nonproductive VJ and V(D)J rearrangements were amplified from individual peripheral CD19+ B cells and were analyzed. No differences in the Vlambda and Jlambda or the VH and JH gene usage in the nonproductive gene repertoire of this SLE patient...
متن کاملA single pre-B cell can give rise to antigen-specific B cells that utilize distinct immunoglobulin gene rearrangements
A group of hybridomas that express antibodies with related specificities for the influenza virus hemagglutinin (HA), that represent B cells that were the clonal progeny of a single pre-B cell, and that utilized distinct L chain gene rearrangements have been characterized. The clonal relationship was established by the sharing of H chain gene rearrangements at both the productive and the nonprod...
متن کاملEfficient antibody diversification by gene conversion in vivo in the absence of selection for V(D)J-encoded determinants.
Antibody diversification in the bursa of Fabricius occurs by gene conversion: pseudogene-derived sequences replace homologous sequences in rearranged immunoglobulin genes. Bursal cells expressing a truncated immunoglobulin mu heavy chain, introduced by retroviral gene transfer, bypass normal requirements for endogenous surface immunoglobulin expression. Immunoglobulin light chain rearrangements...
متن کاملEmploying PCR Technique in Assessment of Monoclonality in Large B-cell Non-Hodgkin\'s Lymphoma
Introduction: Most B-cell malignancies are diagnosed based on morphologic and immunohistochemical criteria. Some cases, however, still present a challenge for the pathologist to discriminate between reactive hyperplasia and neoplastic disorders. Molecular techniques can be used as a helpful diagnostic tool in these cases. In this study, we assessed the value of polymerase chain reaction (PCR) t...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Journal of immunology
دوره 165 2 شماره
صفحات -
تاریخ انتشار 2000