Complement C4 maintains peripheral B-cell tolerance in a myeloid cell dependent manner.

ABSTRACT: The factors that allow self-reactive B cells to escape negative selection and become activated remain poorly defined. Using a BCR knock-in mouse strain, we identify a pathway by which B-cell selection to nucleolar self-antigens is complement dependent. Deficiency in complement component C4 led to a breakdown in the elimination of autoreactive B-cell clones at the transitional stage, characterized by a relative increase in their response to a range of stimuli, entrance into follicles, and a greater propensity to form self-reactive GCs. Using mixed BM chimeras, we found that the myeloid compartment was sufficient to restore negative selection in the autoreactive mice. A model is proposed in which in the absence of complement C4, inappropriate clearance of apoptotic debris promotes chronic ac

SUBMITTER: Chatterjee P 

PROVIDER: S-EPMC4086186 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature