CVID is a multifactorial antibody deficiency that can be associated with autoimmunity, which some studies have proposed to be secondary to altered CD21 expression.
Cross-linking-induced BCR endocytosis was decreased in the IgM(+) memory B cells, especially in those with a CD21(low) phenotype, but not in the naive B cells of patients with CVID with CD21(low) expansion.
The CD21(low) V(H)1-69(+) B cells of MC patients, like those of CVID and HIV patients, are anergic to BCR and TLR9 stimulation and display deregulation of several anergy-related genes; proliferative anergy is also observed in CD21(high) MZ-like V(H)1-69(+) B cells, that over-express the antiproliferative transcriptional repressor Stra13.
Functionally exhausted and mostly autoreactive B-cells with a peculiar CD21(low)CD11c(+) phenotype accumulate in several human immunological disorders including common variable immunodeficiency, HIV infection and rheumatoid arthritis.
The CD21(low) B cells have been shown to be profoundly anergic, and defects of BCR-mediated calcium signaling and of T cells have been described in CVID 1a.
The CD21 B-cell subpopulation in CVID has been intensively characterized by us and other groups and is now better understood leaving their true nature and origin however still obscure.
A majority of CD21(-/lo) B cells from RA and CVID patients expressed germline autoreactive antibodies, which recognized nuclear and cytoplasmic structures.
Consistent with previous studies, we have described two groups of patients with normal (CVID-21norm) or increased (CVID-21lo) proportions of CD27(neg)CD21(neg)CD38(neg) B cells.
Thus, a subgroup of patients with common variable immunodeficiency (CVID) presents with an extraordinary expansion of an unusual B cell population characterized by the low expression of CD21.