Journal Article

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

Szeponik, Louis, Livingston, Megan, Yrlid, Ulf, Wenzel, Ulf Alexander, Bryder, David, Lu, Qianjin, Alsén, Samuel, Karlsson, Joakim, Deng, Yaxiong, Cervin, Jakob, Cucak, Helena, Johansson-Lindbom, Bengt

2022

Overview

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 α 4 β 7 + 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 α 4 β 7 + 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.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Animals / Antigen presentation / B cells / B-Lymphocytes / Bcl-6 protein / bcl6 expression / Blood / Bone marrow / Cell interactions / Cell lineage / Cells / CXCR5 protein / dendritic cells / differentiation / dynamics / Effector cells / efferent lymph / Flow cytometry / follicular-helper / generation / Germinal Center / Germinal centers / gut-homing CD4(+) T cells / Helper cells / Immunization / Immunologi inom det medicinska området / Immunology / Immunology in the Medical Area / induction / Interleukin 4 / interleukin-21 / intestinal lamina propria / Lymph nodes / Lymphocytes B / Lymphocytes T / Major histocompatibility complex / Mice / PD-1 protein / Receptors, CXCR5 - genetics / small / small intestinal lamina propria / Small intestine / subsets / T cells / T-Lymphocytes, Helper-Inducer / Thoracic duct