Cytokine receptors and B cell functions. I. Recombinant soluble receptors specifically inhibit IL-1- and IL-4-induced B cell activities in vitro.
IL-1 and IL-4 are important mediators of B cell growth and differentiation. The cell-surface receptors for these cytokines have recently been cloned and recombinant soluble receptors have been produced that bind their respective ligand. The ability of soluble forms of the murine IL-1R (sIL-1R) and IL-4R (sIL-4R) to inhibit B cell functions in vitro was examined. Proliferation of B cells treated with anti-Ig plus IL-1 or IL-4 was inhibited by the appropriate soluble receptor. sIL-4R also inhibited IL-4-dependent B cell differentiation as measured by: induction of IgG1 and IgE secretion by LPS blasts, down-regulation of IgG3 secretion by LPS blasts, increased Ia expression, and increased Fc epsilon R (CD23) expression. The inhibitory effects of the soluble receptors were found to be highly specific in that sIL-4R had no effect on IL-1-induced B cell activity and sIL-1R had no effect on IL-4 activity, further demonstrating the existence of two independent pathways of B cell activation directed by IL-1 and IL-4.
Maliszewski
C R
CR
Department of Immunology, Immunex Corporation, Seattle, WA 98101.
Sato
T A
TA
Vanden Bos
T
T
Waugh
S
S
Dower
S K
SK
Slack
J
J
Beckmann
M P
MP
Grabstein
K H
KH
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D001402:B-Lymphocytes / Q000502:physiology*; D001667:Binding, Competitive; D002454:Cell Differentiation; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007136:Immunoglobulins / Q000378:metabolism; D007375:Interleukin-1 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D011961:Receptors, Fc / Q000032:analysis; D017455:Receptors, IgE; D011971:Receptors, Immunologic / Q000502:physiology*; D017472:Receptors, Interleukin-1; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000502:physiology*; D011994:Recombinant Proteins; D012995:Solubility
D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D007136:Immunoglobulins; D007375:Interleukin-1; D011961:Receptors, Fc; D017455:Receptors, IgE; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D011994:Recombinant Proteins; D015847:Interleukin-4