Lack of allelic exclusion permits autoreactive B cells to escape deletion.
The R4A-gamma 2b transgenic mouse harbors the gene for the gamma 2b heavy chain of an anti-dsDNA Ab. Approximately 80% of B cells expressing the transgene display allelic exclusion. Although the transgenic mice have little to no detectable serum anti-DNA activity, splenic B cells can be stimulated in vitro with LPS to secrete anti-DNA Ab. Hybridomas derived from LPS-stimulated splenic B cells were analyzed for expression of the transgene and for DNA binding. All nine transgene-encoded anti-DNA-producing lines were found to express an endogenous IgM heavy chain. Of 19 randomly selected lines producing a transgene-encoded non-DNA binding Ab, none expressed a second heavy chain. The tight correlation between lack of allelic exclusion and anti-dsDNA specificity provides strong support for the hypothesis that a major function of allelic exclusion is to prevent the maintenance of a pool of potentially activatable autoreactive cells.
Iliev
A
A
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461.
Spatz
L
L
Ray
S
S
Diamond
B
B
D000483:Alleles; D000818:Animals; D000974:Antibodies, Antinuclear / Q000235:genetics* / Q000276:immunology; D000918:Antibody Specificity; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D015870:Gene Expression; D005803:Genes, Immunoglobulin; D006825:Hybridomas; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics
D000974:Antibodies, Antinuclear; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012333:RNA, Messenger