Søren Egedal Degn

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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Priyadarshini Chatterjee, Program in Cellular and Molecular Medicine, Childrens Hospital, Boston, MA, USA.
  • ,
  • Amma F Agyemang
  • ,
  • Marat B Alimzhanov
  • ,
  • Søren Egedal Degn
  • Stefanos A Tsiftsoglou
  • ,
  • Elisabeth Alicot
  • ,
  • Sarah A Jones
  • ,
  • Minghe Ma
  • ,
  • Michael C Carroll
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
JournalEuropean Journal of Immunology
Pages (from-to)2441-50
Number of pages10
Publication statusPublished - Sept 2013

    Research areas

  • Animals, Apoptosis, Autoantigens, Autoimmunity, B-Lymphocytes, Bone Marrow Cells, Complement C4, Immune Tolerance, Lupus Erythematosus, Systemic, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Knockout, Myeloid Cells, Nucleolus Organizer Region, Receptors, Antigen, B-Cell, Ribonucleoproteins

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