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

Priyadarshini Chatterjee, Amma F Agyemang, Marat B Alimzhanov, Soren E Degn, Stefanos A Tsiftsoglou, Elisabeth M Alicot, Sarah A Jones, Minghe Ma, Michael C Carroll

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32 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)2441 - 2450
Number of pages10
JournalEuropean Journal of Immunology
Volume43
Issue number9
DOIs
Publication statusPublished - 2013

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