Abstract
Abstract Immunoglobulin A (IgA) is the most abundant immunoglobulin in the body and is responsible for maintaining homeostasis at mucosal surfaces. Gut microbes elicit continuous germinal center (GC) reactions within gut associated lymphoid tissues (GALT), which in turn contribute to anti-microbial IgA production by promoting maturation and IgA class switching of B cells that populate the gut lamina propria. Dysregulation of IgA levels is a common disease of unknown etiology. Thus, a better understanding of the mechanisms regulating IgA is critical. We previously found that NK1.1+ cells suppress GC responses and generation of long-lived humoral immunity during systemic viral infection of mice. In the GALT, these NK1.1+ cells may be conventional natural killer cells, group 1 innate lymphoid cells, or natural killer T cells. Surprisingly, systemic depletion of NK1.1+ cells in uninfected specific pathogen free (SPF) mice resulted in an increase in the numbers of GC B cells and T follicular helper cells within GALT (e.g. mesenteric lymph nodes) but not peripheral lymph nodes. In addition, the concentration of IgA in fecal pellets was increased following depletion of NK1.1+ cells when compared to non-depleted control mice. Together our data suggests that an NK1.1-expressing leukocyte inhibits IgA production by impairing GALT GC responses against the gut microbiota. This novel immunoregulatory mechanism may control intestinal homeostasis and prevent development of IgA nephropathy.
Published Version
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