Circulating phenotypic B-1 cells are decreased in common variable immunodeficiency and correlate with immunoglobulin M levels

B-1 cells are innate-like lymphocytes characterized by spontaneous production of 'natural' polyspecific antibodies, often of self-specificity, and thought to be responsible for tissue homeostasis, mucosal protection, maintaining resting serum immunoglobulin (Ig)M levels and for early immunoglobulin production following infection. Although defined most clearly in mice, a human B-1 cell counterpart, defined by the phenotype CD19 or 20⁺CD27⁺CD43⁺CD69 or 70^-, has been proposed recently, facilitating a study of their role in human humoral immunodeficiencies, such as common variable immunodeficiency (CVID). This study examined circulating B-1 cells in 27 CVID patients in comparison to age-matched controls (n=28). Phenotypic putative B-1 cell proportions varied widely, but there was an overall 60-70% decrease in CVID (0·039±0·033% of lymphocytes, mean±standard deviation) compared with controls (0·110±0·159% of lymphocytes, P=0·0012). This decrease was, however, explained largely by concomitant loss of total CD27⁺ memory B cells characteristic of CVID, although those with higher memory B cell proportions appeared to show a true decrease. No age-related effects were apparent in B-1 cell proportions. However, among CVID patients, there was a strong positive correlation between the B-1 cell proportion and serum IgM levels, a relationship that was not evident for IgA, nor was there a relationship between memory B cell proportions and serum IgM. Patients with CVID have fewer circulating putative phenotypic B-1 cells, which largely reflected the overall decrease in memory B cells. However, B-1 cell proportions correlated with resting serum IgM levels, suggesting a possible role in IgM deficiency in CVID.