Antigen-Presenting B Cells Program the Efferent Lymph T Helper Cell Response

Abstract

B cells interact with T follicular helper (Tfh) cells in germinal centers (GCs) to generate high-affinity antibodies. Much less is known about how cognate T–B-cell interactions influence Th cells that enter circulation and peripheral tissues. Therefore, we generated mice lacking MHC-II expressing B cells and, by thoracic duct cannulation, analyzed Th cells in the efferent lymph at defined intervals post-immunization. Focusing on gut-draining mesenteric lymph nodes (MLNs), we show that antigen-specific α4β7+ gut-homing effector Th cells enter the circulation prior to CXCR5+PD-1+ Tfh-like cells. B cells appear to have no or limited impact on the early generation and egress of gut-homing Th cells but are critical for the subsequent appearance of Tfh-like cells that peak in the lymph before GCs have developed. At this stage, antigen-presenting B cells also reduce the proportion of α4β7+ Th cells in the MLN and efferent lymph. Furthermore, cognate B-cell interaction drives a broad transcriptional program in Th cells, including IL-4 that is confined to the Tfh cell lineage. The IL-4-producing Tfh-like cells originate from Bcl6+ precursors in the LNs and have gut-homing capacity. Hence, B cells program the efferent lymph Th cell response within a limited window of time after antigenic challenge.

Are BCL6 and EZH2 novel therapeutic targets for systemic lupus erythematosus?

“…Although the pathological basis and risk factors for SLE have been extensively investigated, the exact pathogenesis of SLE remains to be explored. However, there is increasing evidence that T-cell−B-cell interactions promote the development of SLE, resulting in the generation of high-affinity antibodies [ 1 ]. Tfh cells, a subgroup of T cells, can promote the formation of germinal centers, the maturation of B cells, and the differentiation of plasma cells [ 2 ].…”