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BAFF-driven B cell hyperplasia underlies lung disease in common variable immunodeficiency.

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Area of Science:

  • Immunology
  • Pulmonology
  • Cell Biology

Background:

  • Common variable immunodeficiency (CVID) is a primary immunodeficiency.
  • Interstitial lung disease (ILD) frequently complicates CVID, with unknown causes and limited therapies.

Purpose of the Study:

  • To investigate the role of B cell dysregulation in CVID-ILD progression.
  • To explore the efficacy of rituximab and identify mechanisms of disease recurrence.

Main Methods:

  • Analysis of blood and lung samples from CVID-ILD patients.
  • B cell culture, flow cytometry, ELISA, and histology.
  • Treatment of 11 CVID-ILD patients with rituximab for 18 months.

Main Results:

  • Serum IgM levels correlated with ILD progression and B cell follicle IgM production in the lungs.
  • Rituximab treatment initially improved CVID-ILD but relapse occurred with rising IgM.
  • Elevated B cell-activating factor (BAFF) and BAFF-producing monocytes were found in progressive ILD.
  • BAFF promoted naive B cell survival by increasing anti-apoptotic Bcl-2 expression via BAFF-R.

Conclusions:

  • CVID-ILD is driven by pulmonary B cell hyperplasia.
  • Serum IgM elevation reflects this hyperplasia.
  • Rituximab offers temporary relief, but elevated BAFF promotes B cell survival and disease recurrence.