Linking CD38 Cell Surface Expression to the Unique Calcium Flux Properties in Human Peripheral B Lymphocytes...

CD38 serves as a marker for defining subsets of immune cells; however, being an ectoenzyme, it also plays a crucial part in modulating immunometabolic homeostasis, has immense potential to influence the microenvironment of tissues, functions as a prognostic indicator, as well as a therapeutic target. Despite the extensive information on CD38 and the scale of efforts in developing and optimizing therapies targeting various B cell-related diseases, there is still ongoing fundamental research addressing its basic functions on healthy human B cells, which is well needed. Using an adapted methodology to measure and analyze intracellular Ca²⁺ concentration changes in B cells upon anti-Ig activation, this study describes the possible effect of CD38 cell surface expression on the rapid Ca²⁺ flux response of different B cell subsets from healthy individuals, aiming to better understand the role and influence of CD38 on B cell behavior. Circulating B cell subpopulations bearing IgM type BCRs showed marked differences in their Ca²⁺ flux characteristics according to their respective expression levels of CD38, with the CD38^high transitional cells being visibly different from their transitional and naïve CD38⁺ and CD38^- counterparts, and the unswitched CD38^- cells being clearly distinct based on their Ca²⁺ flux pattern from the CD38⁺ cells in the same compartment, in a setting where CD38 expression was the sole differentiating factor among the subpopulations. The CD38^- unswitched cells had the highest maximum Ca²⁺ concentration among the IgM-expressing populations achieved during anti-IgM stimulation. IgG⁺ class-switched memory cells were clustered uniformly by their activation patterns, showed strong responses to anti-IgG stimulation, with no significant correlations to CD38 expression levels. While our research could not fully separate the functional effects of CD38, this work revealed descriptive data concerning the differential kinetic Ca²⁺ responses of circulating B cells, categorized by their CD38 expression levels.