Feedback suppression of the immune response in vitro. I. Activity of antigen-stimulated B cells.

Abstract

Powerful and often complex regulatory mechanisms that maintain homeostasis are a sine qua non of all carefully studied physiologic activities. Thus, it is not surprising that the immune system has evolved a sophisticated regulatory apparatus for preventing excessive responses to antigenic stimulation. The specific mechanisms so far described include (a) classical antibody feedback which is believed to operate by interference with cellular recognition of antigenic determinants (1, 2) and (b) development of suppressor T lymphocytes (Ts) 1 (3, 4), recognizing either antigenic (5) or idiotypic (6) determinants and functioning in part by the release of subcellular effector molecules (7-10). Until now, these two broad categories have been considered as largely independent pathways. However, it would seem likely that to most efficiently control humoral immunity, some interrelationship between these modalities would have evolved.The initial purpose of these studies was to further characterize the triggering and mode of action of suppressor T cells and T-suppressor factors (T+F). Previous data have shown that Ts play a major role in the regulation of the Ir gene-controlled response to L-glutamic acid6°-L-alaninea°-L-tyrosine l° (GAT): GAT priming of nonresponder mice leads primarily to stimulation of GAT-specific T~ (11), which produce a soluble GAT TsF factor (GAT-TsF) (9) bearing I-region determinants and sharing a common idiotype with anti-GAT antibodies (12) that stimulates virgin T cells to develop T~ activity (GAT-T+F-induced Ts [T~]) (13). Furthermore, similar T~ and T+F can be obtained from responder lymphocytes, provided that antigen-presenting adherent cells are removed before GAT exposure (14).

Chronic schistosome infection leads to modulation of granuloma formation and systemic immune suppression

“…The realization that B cells have regulatory capacity was initially demonstrated in response to sheep red blood cells and was associated first with regulatory antibody production and later linked to interactions with T cells (Stockinger et al, 1979; Zubler et al, 1980). Subsequent studies in mice and humans have demonstrated that B lymphocytes can regulate immune responses through antibody-dependent mechanisms as well as via direct cell–cell interactions and regulatory cytokine production (Klinker and Lundy, 2012).…”

Experimental models of B cell tolerance in transplantation

“…B cells with the capacity to regulate T cell function were originally described by Shimamura et al (69–71) and independently by Zubler et al (72, 73) over 30 years ago. In a system of high dose (4 × 10^9) SRBC into C57BL/6 mice, Shimamura et al (71) reported that splenic B cells were able to induce antigen-specific suppressor T cells that subsequently inhibited B cells responses.…”

Immunoregulatory Effect of Antibody on Delayed-Type Hypersensitivity in Mice

“…Recently, immune B cells have been re ported to help in the regulation of the humoral im mune response and contact sensitivity [5][6][7][19][20][21][22][23]. For those experimental systems, it seemed that the suppressor activities of immune B cells were mediated via antibodies, and thus that possibly the idiotypeantiidiotype network was involved.…”