B-cell maturation and antibody responses in individuals carrying a mutated CD19 allele

Abstract

Homozygous CD19 mutations lead to an antibody deficiency due to disruption of the CD19 complex and consequent impaired signaling by the B-cell antigen receptor. We studied the effects of heterozygous CD19 mutations on peripheral B-cell development and antibody responses in a large family with multiple consanguineous marriages. Sequence analysis of 96 family members revealed 30 carriers of the CD19 mutation. Lymphocyte subset counts were not significantly different between carriers and noncarriers in three different age groups (0-10 years; 11-18 years; adults). B cells of carriers had reduced CD19 and CD21 median expression levels, and had reduced proportions of transitional (0-10 years) and CD5 þ B cells (adults). CD19 carriers did not show clinical signs of immunodeficiency; they were well capable to produce normal serum Ig levels and had normal responses to primary and booster vaccinations. The frequency of mutated Vk alleles was not affected. Heterozygous loss of CD19 causes some changes in the naive B-cell compartment, but overall in vivo B-cell maturation or humoral immunity is not affected. Many antibody deficiencies are not monogenetic, but likely caused by a combination of multiple genetic variations. Therefore, functional analyses of immune cell function should be carried out to show whether heterozygous mutations contribute to disease.

CD19 controls Toll-like receptor 9 responses in human B cells

“…All CD19-deficient patients and CD19-heterozygous carriers have been described (9, 23). The specific mutations in BTK have been previously reported in the following family members: XLA 022 (24) and XLA 596, XLA 796 (25).…”

New frontiers of primary antibody deficiencies

“…In man, genetic defects in the CD19 or CD81 genes have been shown to result in an antibody deficiency syndrome [48,49,52,96]. B cells from CD19-deficient and CD81-deficient patients have impaired Ca 2?…”

A case of progressive multifocal leukoencephalopathy in a lupus patient treated with belimumab – comments on article by Fredericks et al.

“…In fact, genetic deficiencies of CD19 expression (or its coordinated protein CD81) have been described [2][3][4][5] which were reported in association with autoimmune diseases including SLE. 2,3,6 In some cases alteration of CD19 B cells' surface expression was even hypothesized to play a role in the pathogenesis of SLE.…”

“…2,4,5 It is worthy to note that abnormalities in CD19 expression were found to affect transitional B cells, 5 which are likely to be the most susceptible to belimumab treatment, therefore a congenital deficiency in CD19 levels would expose patients to an unexpectedly great decrease in transitional B cells.…”