TIM-4 identifies effector B cells expressing an IL-23-driven proinflammatory cytokine module that promotes immune responses

Abstract

B cells can express pro-inflammatory cytokines that promote a wide variety of immune responses. Here we show that B cells expressing the phosphatidylserine receptor TIM-4, preferentially express IL-17A, as well as IL-22, IL-6, IL-1{beta}, and GM-CSF - a pattern of cytokines reminiscent of pathogenic Th17 cells. Expression of this proinflammatory module requires IL-23R signaling and selective expression of ROR{gamma}t by TIM-4+ B cells. TIM-4+ B cell-derived-IL-17A not only enhances the severity of experimental autoimmune encephalomyelitis (EAE) and promotes allograft rejection but also acts in an autocrine manner to prevent their conversion into IL-10-expressing B cells with regulatory function. Thus, IL-17A acts as an inflammatory mediator and enforces the proinflammatory activity of TIM-4+ B cells. Moreover, TIM-4 serves as a broad marker for ROR{gamma}t-expressing effector B cells (Beff). These findings allow further study of the signals regulating Beff differentiation and effector molecule expression.