Quorum sensing contributes to activated B cell homeostasis and to prevent autoimmunity

TL;DR

This study uncovers a quorum sensing mechanism involving IgG sensing via FcγRIIB that regulates activated B cell homeostasis and prevents autoimmunity by controlling IgM-secreting B cell populations.

Contribution

It reveals a novel B cell regulation pathway where IgG sensing modulates B cell activation, distinct from previous competition-based mechanisms.

Findings

IgG sensing via FcγRIIB regulates B cell activation.

Disruption of this pathway may lead to autoimmunity.

B cell homeostasis involves monitoring secreted products, not just niche competition.

Abstract

Maintenance of plasma IgM levels is critical for immune system function and homeostasis in humans and mice. However, the mechanisms that control homeostasis of the activated IgM-secreting B cells are unknown. After adoptive transfer into immune-deficient hosts, B-lymphocytes expand poorly but fully reconstitute the pool of natural IgM-secreting cells and circulating IgM levels. By using sequential cell transfers and B cell populations from several mutant mice, we were able to identify novel mechanisms regulating the size of the IgM-secreting B cell pool. Contrary to previous mechanisms described regulating homeostasis, which involve competition for the same niche by cells having overlapping survival requirements, homeostasis of the innate IgM-secreting B cell pool is also achieved when B cells populations are able to monitor the number of activated B cells by detecting their secreted products. Notably, B cell populations are able to assess the density of activated B cells by sensing their secreted IgG. This process involves the Fc{\gamma}RIIB, a low-affinity IgG receptor that is expressed on B cells and acts as a negative regulator of B cell activation, and its intracellular effector the inositol phosphatase SHIP. As a result of the engagement of this inhibitory pathway the number of activated IgM-secreting B cells is kept under control. We hypothesize that malfunction of this quorum-sensing mechanism may lead to uncontrolled B cell activation and autoimmunity.