Dataset Information


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 activation of myeloid cells, allowing the maturation and activation of self-reactive B-cell clones leading to increased spontaneous formation of GCs.

SUBMITTER: Chatterjee P 

PROVIDER: S-EPMC4086186 | BioStudies | 2013-01-01

REPOSITORIES: biostudies

Similar Datasets

2020-01-01 | S-EPMC7927756 | BioStudies
2017-01-01 | S-EPMC5784431 | BioStudies
2017-01-01 | S-EPMC5601957 | BioStudies
2012-01-01 | S-EPMC3458355 | BioStudies
2019-01-01 | S-EPMC6461443 | BioStudies
2019-01-01 | S-EPMC7015177 | BioStudies
1989-01-01 | S-EPMC1138525 | BioStudies
2016-01-01 | S-EPMC5108556 | BioStudies
1980-01-01 | S-EPMC1161918 | BioStudies
2010-01-01 | S-EPMC3567757 | BioStudies