Plasma cells negatively regulate the follicular helper T cell program

Abstract

B lymphocytes differentiate into antibody-secreting cells under the antigen-specific control of follicular helper T (TFH) cells. Here, we demonstrate that isotype-switched plasma cells expressed MHCII, CD80 and CD86 and intracellular machinery required for antigen presentation. Antigen-specific plasma cells could access, process and present sufficient antigen in vivo to induce multiple TH cell functions. Importantly, antigen-primed plasma cells failed to induce interleukin 21 or Bcl-6 in naïve TH cells and actively shut down these key molecules in antigen-activated TFH cells. Mice lacking plasma cells displayed altered TFH activity, providing evidence for this negative feedback loop. Hence, antigen presentation by plasma cells defines a new layer of cognate regulation that limits the antigen-specific TFH program controlling ongoing B cell immunity.