International Immunology, Vol. 4, No. 1, pp. 15-21,January 1992
© 1992 Japanese Society for Immunology
Can peritoneal B cells be rendered unresponsive?
Immunology and Immunotherapy Division, University of Rochester Cancer Center Rochester, NY 14642, USA
Department of Microbiology and Immunology, University of Rochester School of Medicine Rochester, NY 14642, USA
Correspondence to: Correspondence to: D.W. Scott
Ly-1+ B cells have been reported to produce a number of autoantibodies, and to be involved in the selection and regulation of the conventional B cell repertoire. It is not known if these B cells, which are found in high numbers in the peritoneum of normal adult mice, themselves can be regulated. In this study, we evaluated the sensitivity of peritoneal B cells (PBCs) versus conventional splenic B cells to regulation in a model system for tolerance. Normal splenic (conventional) or PBCs (containing both CD5+ and CD5– ‘sister’ cells) were cultured overnight with either F(ab’)2 or intact IgG anti-mouse Ig, washed, and then challenged with fluorescein(FL)-coupled to Brucella abortus (BA), trlmethylammonium (TMA)-BA or lipopolysaccharide (LPS), and the IgM responses to the FL and TMA haptens measured. In contrast to spleen cells, which exhibited up to a 90% reduction in anti-FL responsiveness, pretreated PBCs were mostly resistant to this form of tolerance regardless of challenge. The anti-TMA response of PBCs, which reflects the skewed VH11 usage by peritoneal CD5 B cells, was also resistant to tolerance. However, spienic TMA-specific B cells appeared to be sensitive to unresponsiveness induced by anti-lg. Signaling studies show that PBCs have a blunted initial Ca2+ response, suggesting that the consequence of anti-lg crosslinklng may be defective in these cells. Furthermore, phorbal myristate acetate and/or lonomycln treatment of both PB and splenic B cells led to hyporesponsiveness to LPS challenge. This suggests that PBCs may be defective in a signalling pathway, perhaps involving protein klnase C activation. Our studies reveal that antibody production by PBCs is not subject to conventional tolerance pathways, a control which may be Important in terms of their ability to regulate other B cells.
Keywords: B cell tolerance, CD5, peritoneal B cells
1Present address: Immunotoxicology, Bristol-Myers Squibb Co., Box 4755, Syracuse, NY 13221-4755, USA
Received 2 August 1991, accepted 28 September 1991.
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