Multiple signaling pathways mediate anti-Ig and IL-4-induced early response gene expression in human tonsillar B cells.

Abstract:

:We have analyzed the relationship between the signaling pathways coupled to surface immunoglobulin and interleukin (IL)-4 receptors in human B cells from the patterns of expression of a panel of phorbol ester-inducible early response genes (ERG) activated by anti-IgM and IL-4 stimulation in vitro. Anti-IgM stimulation led to the induction of all eleven ERG tested. Two of these, the proto-oncogene, c-fos and an anonymous ERG 1R20 were insensitive to protein kinase C (PKC) inhibition with the drug, staurosporine and retained inducibility after down-regulation of PKC activity by purging with phorbol ester. These observations are consistent with previous data showing anti-IgM signaling through both PKC-dependent and PKC-independent pathways. c-fos and 1R20 were also the only ERG inducible in response to IL-4 stimulation and whilst ionomycin induced only c-fos, dibutyryl cyclic adenosine monophosphate stimulation led to induction of both c-fos and 1R20. These observations lend support to a role for the adenylate cyclase pathway being important for coupling of IL-4-generated signals to B cells responses. None of the anti-IgM-responsive ERG was further induced when B cells were co-stimulated with a combination of anti-IgM and IL-4, suggesting that the signaling cascades from these two agents are integrated downstream of third messenger pathways to synergistically promote B cell proliferation.

journal_name

Eur J Immunol

authors

Murphy JJ,Norton JD

doi

10.1002/eji.1830231122

subject

Has Abstract

pub_date

1993-11-01 00:00:00

pages

2876-81

issue

11

eissn

0014-2980

issn

1521-4141

journal_volume

23

pub_type

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