In:
European Journal of Immunology, Wiley, Vol. 43, No. 9 ( 2013-09), p. 2441-2450
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 C 4 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 GC s. 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 C 4, 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 GC s.
Type of Medium:
Online Resource
ISSN:
0014-2980
,
1521-4141
DOI:
10.1002/eji.201343412
Language:
English
Publisher:
Wiley
Publication Date:
2013
detail.hit.zdb_id:
1491907-2