CD11c+ B Cells Are Mainly Memory Cells, Precursors of Antibody Secreting Cells in Healthy Donors

Abstract

CD11c + B cells have been reported to be increased in autoimmune diseases, but they are detected in the blood of healthy individuals as well. We aimed to characterize CD11c + B cells from healthy donors by flow cytometry, microarray analysis, and in vitro functional assays. Here, we report that CD11c + B cells are a distinct subpopulation of B cells, enriched in the memory subpopulation even if their phenotype is heterogeneous, with overexpression of genes involved in B-cell activation and differentiation as well as in antigen presentation. Upon activation, CD11c + B cells can differentiate into antibody-secreting cells, and CD11c could be upregulated in CD11c − B cells by B-cell receptor activation. Finally, we show that patients with pemphigus, an autoimmune disease mediated by B cells, have a decreased frequency of CD11c + B cell after treatment, relative to baseline. Our findings show that CD11c + B cells are mainly memory B cells prone to differentiate into antibody secreting cells that accumulate with age, independently of gender.

Activated Human Memory B Lymphocytes Use CR4 (CD11c/CD18) for Adhesion, Migration, and Proliferation

“…While various characteristics of CD11c + blood derived B cells were described recently by Golinski et al ( 13 ), the genuine role of CR4 expressed on B cells activated via a physiological stimulus has not been clarified yet. To this end, we decided to reveal the function of this β 2 integrin in adhesion, proliferation, and migration on BCR activated human B lymphocytes.…”

“…At the same time, the frequency of CD11c + B cells was reduced in the naïve (CD27 − IgD + ) as well as in the double negative (CD27 − IgD − ) population. Yet, CD11c was detected in each subpopulation suggesting a role for CR4 in all steps of B-cell development ( 13 ). Since the phenotype of tonsil derived CD11c + human B cells has not been defined so far, we set out to characterize this population.…”

“…However, the available data regarding the appearance and certain functions of CR3 and CR4 on human B cells are rather inconsistent [reviewed in ( 1 )]. Ehrhardt et al showed that the expression of these receptors is mutually exclusive ( 16 ), while in a very recent study, Golinski et al showed that the CD11b mRNA can be upregulated in CD11c + B cells ( 13 ).…”

“…In contrast to the ever-growing information of their role in myeloid cell types, our knowledge about the expression and function of CR3 and CR4 on human B lymphocytes is limited. Though these two receptors are not widely expressed on non-activated B lymphocytes of healthy donors ( 7 , 8 ), they can be detected on certain B cell populations or after activation by different stimuli ( 7 , 9 – 13 ). Regarding their function, CR3 was shown to contribute to the high migratory potential of the CD11b + B lymphocytes, potentially helping inflammatory processes ( 12 , 14 ), while CR4 was demonstrated to be involved in the adhesion and proliferation of PMA stimulated B cells ( 7 ).…”

“…Regarding their function, CR3 was shown to contribute to the high migratory potential of the CD11b + B lymphocytes, potentially helping inflammatory processes ( 12 , 14 ), while CR4 was demonstrated to be involved in the adhesion and proliferation of PMA stimulated B cells ( 7 ). Recently, Golinski et al demonstrated that CD11c + B cells differentiate into antibody-secreting cells upon activation, however the role of CR4 in this process was not clarified ( 13 ).…”