Skewed VH and V kappa gene family expression and pairing occurs among B lymphocytes in autoimmune motheaten mice.
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).
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Related Subject Headings
- Recombinant Proteins
- Multigene Family
- Mice, Mutant Strains
- Mice, Inbred C57BL
- Mice
- Lymphocyte Activation
- Lipopolysaccharides
- Interleukin-4
- Immunology
- Immunoglobulin kappa-Chains
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Recombinant Proteins
- Multigene Family
- Mice, Mutant Strains
- Mice, Inbred C57BL
- Mice
- Lymphocyte Activation
- Lipopolysaccharides
- Interleukin-4
- Immunology
- Immunoglobulin kappa-Chains