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STUDY OF CONGENITALLY IMMUNOLOGIC MUTANT NEW ZEALAND MICE: V. B CELL FUNCTION OF NZB‐X ld MICE
Author(s) -
Ohsugi Y.,
Gershwin M. E.,
Ahmed A.
Publication year - 1981
Publication title -
international journal of immunogenetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.41
H-Index - 47
eISSN - 1744-313X
pISSN - 1744-3121
DOI - 10.1111/j.1744-313x.1981.tb00750.x
Subject(s) - biology , b cell , microbiology and biotechnology , spleen , bruton's tyrosine kinase , antibody , idiotype , immunology , lymphocyte , c57bl/6 , immunoglobulin m , immunoglobulin d , phytohaemagglutinin , immunoglobulin g , genetics , tyrosine kinase , monoclonal antibody , signal transduction
Summary NZB mice bearing the CBA/N X chromosome linked defect were generated by repetitive backcrossing and selection of the X ld gene. The male offspring resulting from the cross of NZB with CBA/N were selected as being X ld Y on the basis of sera IgM and IgG 3 levels and responsiveness to DNP‐Lys‐Ficoll. Following this inbreeding protocol, 6th generation backcross NZB X ld Y mice were compared to littermate controls with respect to B cell function. Sera immunoglobulin levels of IgG 1 , IgG 2a , IgG 2b and IgA were similar in X ld Y and XY mice. In contrast, levels of IgM and IgG 3 , from X ld Y mice were approximately 15% and 50%, respectively, of values found in littermates. Furthermore, X ld Y mice failed to respond to DNP‐Lys‐Ficoll and had less than 3% splenic Lyb 5.1‐bearing cells. Splenic immunoglobulin cell surface profiles, obtained by the fluorescent activated cell sorter, indicated a significant reduction in the frequency of Ig bearing cells in X ld animals. Such profiles were similar to those obtained for spleen cells from reference control CBA/N mice. Finally, an elevated number of splenic, lymph node and bone marrow background and lipopolysaccharide‐induced B cell clones in semi‐solid phase agar was found in NZB but not C57BL/6, C3H, BALB/c and DBA/2 controls. In contrast, NZB X ld Y mice had virtually no detectable B cell colonies. This data, obtained on significantly inbred X ld Y NZB mice, suggests that the X id gene is dominant over several aspects of polyclonal B cell activation in NZB mice and indicates that serial observation of these mice will be valuable in understanding the interactions of genetic immunologic mutations and cellular function in autoimmunity.