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Complement Factor H Modulates Splenic B Cell Development and Limits Autoantibody Production.

Máté G Kiss1,2, Mária Ozsvár-Kozma1,2, Florentina Porsch1,2

  • 1Department for Laboratory Medicine, Medical University of Vienna, Vienna, Austria.

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|July 30, 2019
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Summary
This summary is machine-generated.

Complement factor H (CFH) deficiency in mice causes B cell accumulation and heightened B cell receptor (BCR) signaling. This leads to splenomegaly, autoimmunity, and increased anti-dsDNA antibodies, suggesting CFH limits BCR activity and prevents autoimmune disease.

Keywords:
B cell developmentB cell receptor signalingautoimmunitycomplementcomplement factor H

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Area of Science:

  • Immunology
  • Complement System
  • B cell Biology

Background:

  • Complement factor H (CFH) regulates complement activation, linking innate and humoral immunity.
  • The role of CFH in B cell biology remains largely unexplored.

Purpose of the Study:

  • To investigate the role of CFH in splenic B cell development and function.
  • To determine the impact of CFH deficiency on B cell receptor (BCR) signaling and autoimmunity.

Main Methods:

  • Analysis of B cell populations in CFH-deficient (Cf h-/-) mice.
  • Assessment of BCR signaling pathways, including phosphorylated Bruton's tyrosine kinase (pBTK) and spleen tyrosine kinase (pSYK).
  • Evaluation of complement consumption, complement receptor 2 (CR2/CD21) expression, spleen architecture, and autoantibody production.

Main Results:

  • CFH deficiency led to altered splenic B cell development with marginal zone (MZ) B cell accumulation.
  • B cells from Cf h-/- mice showed enhanced BCR signaling, increased C3 consumption, and elevated CR2/CD21 levels.
  • Aged Cf h-/- mice developed splenomegaly, distorted spleen architecture, and spontaneous B cell-dependent autoimmunity with germinal center hyperactivity and increased anti-dsDNA antibodies.

Conclusions:

  • CFH acts as a negative regulator of BCR signaling.
  • CFH deficiency promotes B cell hyperactivity and autoimmunity.
  • CFH plays a critical role in preventing spontaneous B cell-driven autoimmune diseases.