Skewed VH and V kappa gene family expression and pairing occurs among B lymphocytes in autoimmune motheaten mice.

Journal Article (Journal Article)

Motheaten mice homozygous for the recessive mev mutation develop a fatal immunodeficiency syndrome associated with hypergammaglobulinemia, thymic aplasia, production of autoantibodies and development of a severe lupus like systemic autoimmune disease. Most B lymphocytes in this mutant strain belong to B-1 subset. We have addressed the question if differences existed in the V-gene repertoire of autoimmune mev/mev mice as compared to phenotypically normal mev/+ and C57BL/6 background strain by examining the VH and V kappa gene family expression as well as the association of VH and V kappa gene families among B lymphocyte clones. The data outlined here demonstrate that both the expression of VH and V kappa gene families and their association is skewed in mev/mev mice, suffering from systemic autoimmune disease, and differs significantly from phenotypically normal mev/+ litter mates as well as the C57BL/6 background strain. In addition, VH+V kappa gene family pairs in phenotypically normal mev/+ differed from normal C57BL/6 mice suggesting that motheaten mutation, whether homozygous or heterozygous, alters the development of the B lymphocyte repertoire. These observations suggest positive selection of B-1 lymphocytes in autoimmune motheaten mice either as a result of selective processes, via receptor-ligand interactions, operating on the development of the primary antibody repertoire or defective B lymphocyte haematopoiesis due to the deficiency of haematopoietic cell phosphatase involved in determining the threshold by which B cells respond to self antigen(s).

Full Text

Duke Authors

Cited Authors

  • Saitoh, Y; Kelsoe, G; Bona, C; Kaushik, A

Published Date

  • 1995

Published In

Volume / Issue

  • 21 / 3

Start / End Page

  • 185 - 193

PubMed ID

  • 8822276

International Standard Serial Number (ISSN)

  • 0891-6934

Digital Object Identifier (DOI)

  • 10.3109/08916939509008015


  • eng

Conference Location

  • England