Induction of B cell activities by interleukin 4 is inhibited by a receptor-specific monoclonal antibody in vitro.
The effects of interleukin (IL) 4 on B cell growth and differentiation are mediated through binding of IL 4 to a specific cell surface receptor. The murine T cell IL 4 receptor (IL 4R) has recently been cloned and monoclonal antibodies (mAb) which bind specifically to the IL 4R have been developed. The ability of two of these anti-IL 4R mAb (M1 and M2) to inhibit IL 4-induced B cell functions in vitro was examined. The M1 mAb inhibited the ability of IL 4 to induce B cell proliferation in a dose-related fashion. The inhibition was specific for proliferation induced by IL 4 in that the antibody did not affect induction of proliferation by IL 1. Similarly, M1 inhibited IL 4-dependent B cell differentiation as measured by induction of IgG1 and IgE secretion, decreased IgG3 secretion, increased Ia expression, and increased Fc epsilon R (CD23) expression. In contrast, the anti-IL 4R-specific mAb M2 had no effect upon any of these activities. The ability of M1 but not M2 to inhibit IL 4-induced B cell growth and differentiation correlated with the inhibition of binding of radiolabeled IL 4 by M1. These reagents should be valuable tools with which to analyze the involvement of IL 4 in immune responses.
Maliszewski
C R
CR
Department of Immunology, Immunex Corporation, Seattle, WA 98101.
Sato
T A
TA
Vanden Bos
T
T
Beckmann
M P
MP
Grabstein
K H
KH
D000818:Animals; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis; D000954:Antigens, Surface / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007136:Immunoglobulins / Q000032:analysis; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D011961:Receptors, Fc / Q000096:biosynthesis; D017455:Receptors, IgE
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface; D000949:Histocompatibility Antigens Class II; D007136:Immunoglobulins; D011961:Receptors, Fc; D017455:Receptors, IgE; D015847:Interleukin-4