Role of T cells in regulating expression of the B cell repertoire. Anti-ssDNA precursor frequency of DBA/2 B cells is increased in the presence of T cells from NZB mice.
Splenic B cells from DBA/2 and NZB mice were compared with regard to precursor frequency of anti-ssDNA-producing cells. Using a modification of the splenic fragment assay, we show that NZB T cells are capable of increasing the frequency of expression of anti-ssDNA precursors in DBA/2 splenic B cells. When limiting numbers of splenic B cells of DBA/2 origin were adoptively transferred into an irradiated (1200 rad) recipient, the co-transfer of NZB T cells markedly increased the frequency of anti-ssDNA precursors in cultured splenic fragments. The anti-ssDNA produced under these conditions was exclusively IgM and exhibited a high degree of cross-reactivity with TNP and fluorescein. Thus, the increase in anti-ssDNA precursor frequency reflected an expansion of the B cell repertoire to include precursors of polyspecific antibody-producing cells that under normal circumstances are not expressed. The ability of NZB T cells to increase the anti-ssDNA precursor frequency was further defined by the CBA/N immunodeficiency gene xid, in that B cells from DBA/2.xid donors did not exhibit increased anti-ssDNA precursor frequency in the presence of NZB T cells. When NZB splenic B cells were co-transferred with DBA/2 T cells, the anti-DNA precursor frequency of the NZB B cells was not reduced. This study demonstrates that T cells can influence the emergency of B cell clones in an Ag-nonspecific manner. The well documented in vivo spontaneous polyclonal activation of NZB B cells may be secondary to T cell-mediated expansion of the B cell repertoire.
Cowdery
J S
JS
Department of Internal Medicine, University of Iowa, College of Medicine, Iowa City 52242.
Pitts
A K
AK
D000818:Animals; D000974:Antibodies, Antinuclear; D001402:B-Lymphocytes / Q000145:classification* / Q000276:immunology / Q000502:physiology; D002450:Cell Communication; D002999:Clone Cells / Q000145:classification / Q000276:immunology; D004277:DNA, Single-Stranded / Q000276:immunology*; D005260:Female; D007958:Leukocyte Count; D051379:Mice; D008811:Mice, Inbred DBA; D008814:Mice, Inbred NZB; D010641:Phenotype; D013045:Species Specificity; D013154:Spleen / Q000166:cytology; D013234:Stem Cells / Q000145:classification* / Q000276:immunology / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000974:Antibodies, Antinuclear; D004277:DNA, Single-Stranded