Microbiota Tune B Cell Autoreactivity
Principal Investigator: Duane Wesemann, Harvard Medical School, Brigham and Women’s Hospital
B cells can play key roles in autoimmunity, but how autoreactive B cells are regulated is not fully understood. Most newly formed B cell receptors (BCRs) are autoreactive, however B cell developmental checkpoints cull most autoreactive BCRs from the repertoire. Autoreactive B cells are often polyreactive. Polyreactive immunoglobulins (Igs) are capable of binding many structurally diverse antigens and therefore can enhance the antigen recognition capacity of any given BCR repertoire, but this comes at a cost increased risk of self-recognition. Our group has recently shown that conventionalization of germ-free mice increases the bacterial recognition capacity by reducing the negative selection of polyreactivity from immature B cell repertoires. Based on these findings, the objective of this proposal is to identify mechanisms through which microbiota influence the frequency of polyreactivity Igs. The project deliverable is the elucidation of a mechanistically link between microbiota and predisposition to autoimmune disease.