Continuous anti-interleukin 10 antibody administration depletes mice of Ly-1 B cells but not conventional B cells.
Ly-1 B cells have the distinctive property of continuous self-replenishment and, as we have shown previously, can be further distinguished from conventional B cells on the basis of greatly elevated constitutive and inducible production of the recently described cytokine interleukin 10 (IL-10). To test the possibility that IL-10 acts as either an autocrine or paracrine growth factor for Ly-1 B cells, we treated mice continuously from birth to 8 wk of age with a monoclonal rat IgM antibody that specifically neutralizes mouse IL-10. Mice treated in this way lacked peritoneal-resident Ly-1 B cells, contained greatly reduced serum immunoglobulin M levels, and were unable to generate significant in vivo antibody responses to intraperitoneal injections of alpha 1,3-dextran or phosphorylcholine, antigens for which specific B cells reside in the Ly-1 B cell subset. In contrast, conventional splenic B cells of anti-IL-10-treated mice were normal with respect to total numbers, phenotype, and in vitro responsiveness to B cell mitogens and the thymus-dependent antigen trinitrophenyl-keyhole limpet hemocyanin (TNP-KLH). The mechanism of Ly-1 B cell depletion appeared to be related to elevation of endogenous interferon gamma (IFN-gamma) levels in anti-IL-10-treated mice, since coadministration of neutralizing anti-IFN-gamma antibodies substantially restored the number of peritoneal-resident Ly-1 B cells in these mice. These results implicate IL-10 as a regulator of Ly-1 B cell development, and identify a procedure to specifically deplete Ly-1 B cells, thereby allowing further evaluation of the role of these cells in the immune system.
Ishida
H
H
DNAX Research Institute, Palo Alto, California 94304.
Hastings
R
R
Kearney
J
J
Howard
M
M
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology*; D017252:CD3 Complex; D002455:Cell Division; D005260:Female; D005455:Fluorescent Antibody Technique; D007075:Immunoglobulin M / Q000097:blood; D007274:Injections, Intraperitoneal; D016753:Interleukin-10 / Q000502:physiology*; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009500:Neutralization Tests; D010641:Phenotype; D011247:Pregnancy; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology
D000906:Antibodies; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D011948:Receptors, Antigen, T-Cell; D016753:Interleukin-10