An alternative pathway of B cell activation: stilbene disulfonates interact with a Cl- binding motif on AEn-related proteins to stimulate mitogenesis.

Abstract:

:Stilbene disulfonates are known to competitively inhibit Cl-/HCO3- flux through Band 3-related anion exchange (AE) proteins. To study the role of AE in lymphocyte activation, stilbene disulfonates were added to cultures of rat splenocytes (SPL). Four different stilbene derivatives were tested and each directly stimulated mitogenic proliferative responses of SPL. The mitogenic activity of these analogs paralleled their known patterns of interaction with Band 3-related AE proteins, as measured by; (a) their effective mitogenic concentrations, (b) their rank order of mitogenic potency [DIDS greater than SITS greater than DNDS congruent to DAzDS], (c) their patterns of nonreversible binding to the mitogenic receptor [DIDS much greater than SITS, DNDS], and (d) the specific, noncompetitive inhibition of their activity by the antagonist niflumic acid. Stilbene disulfonates directly activated purified B cell populations but not isolated T cells and furthermore, acted in synergy with anti-IgM to stimulate proliferation of SPL. These findings show that stilbene disulfonates represent a novel class of mitogens that interact with AEn-related proteins to stimulate an alternative activation pathway in B cells. These studies also indicate that immunomodulating activities of nonsteroidal anti-inflammatory drugs such as niflumic acid may be mediated, in part, by their interactions with AEn-related proteins.

journal_name

Eur J Immunol

authors

Deane KH,Mannie MD

doi

10.1002/eji.1830220509

keywords:

subject

Has Abstract

pub_date

1992-05-01 00:00:00

pages

1165-71

issue

5

eissn

0014-2980

issn

1521-4141

journal_volume

22

pub_type

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