Biphasic effect of kallikrein on IgE and IgG1 syntheses by LPS/IL-4-stimulated B cells.
epsilon receptor modulating protein (epsilon RMP) was identified and purified in our previous studies as a murine T cell-derived soluble 17-kDa chymotryptic serine protease which suppresses avidity of binding between IgE and CD23 (low affinity Fc receptor for IgE) without decreasing the quantitative expression of the CD23 molecule. Some, but not all, of the other known soluble serine proteases showed epsilon RMP-like CD23-modulating activities. Further studies indicated that epsilon RMP exists not only as a soluble protein but also as a 36-kDa T-cell surface form. Both soluble and membrane-bound epsilon RMP can induce purified splenic B cells to secrete IgE in the presence of IL-4 even without lipopolysaccharide (LPS). In this study, therefore, we have tested effects of several known serine proteases on Ig production in vitro and have found that: (i) coculture of splenic B cells in the presence of LPS and IL-4 with serine proteases which have epsilon RMP-like substrate specificity, such as kallikrein and alpha-chymotrypsin, results in a significant increase of IgG1 and a slight increase of IgE secretion at low concentrations, and significant suppression at high concentrations in an isotype-selective manner; and (ii) the effects of these proteases are blocked by phenylmethylsulfonyl fluoride but not by indomethacin, suggesting that serine protease activity but not prostaglandin E2 is involved. The biological significance of the possible involvement of serine proteases on Ig class switching is discussed.
Matsushita
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Division of Immunology, Medical Biology Institute, La Jolla, California 92037.
Katz
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DH
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D006825:Hybridomas; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007213:Indomethacin / Q000494:pharmacology; D015847:Interleukin-4; D007610:Kallikreins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008070:Lipopolysaccharides; D051379:Mice; D008807:Mice, Inbred BALB C; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology
D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D015847:Interleukin-4; D007073:Immunoglobulin E; D010664:Phenylmethylsulfonyl Fluoride; D007610:Kallikreins; D007213:Indomethacin