Altered B cell populations and antibody production within the inflamed colon and gut-associated lymphoid tissues
Milad Sabzevary, Diane M Tshikudi, Sen Hou, Fatemeh Hesampour, Nour Eissa, Charles N Bernstein, Aaron J Marshall, Jean-Eric GhiaAbstract
Background and aims
B cells and plasma cells within gut-associated lymphoid tissues (GALTs) are essential to generate IgA and maintain homeostasis by controlling commensal bacteria and pathogens. We aim to uncover B cell characteristics and antibody production within inflamed GALTs.
Methods
B cell-related transcriptional signatures were assessed in a bulk RNA-sequencing data of colon biopsies from pan-colitic patients and control cases. In preclinical mouse model experiments, B cell subsets in GALTs were analyzed using flow cytometry and immunofluorescence microscopy. Expression of cytokines and immunoglobulin class-switch transcripts were measured by qRT-PCR. Antibody subclasses and reactivity to self-antigens in colonic lumen were measured using ELISA and autoantigen microarray.
Results
In pan-colitic patients, there was an enrichment for B cell-related genes and upregulation of activating and recruiting B cells. In colitic mice, immunostaining demonstrated aggregation of CD19+B220+ B cells within the colon lamina propria that were largely IgD+. Flow cytometry analyses revealed significant increases in B cells within colon and mesenteric lymph nodes, as well as increased expression of CD86. In colitic mice, colonic IgM antibody levels increased, along with evidence suggesting elevated self-antigen reactivity of IgM and IgG, but not IgA.
Conclusions
Acute intestinal inflammation leads to expression of factors driving B cell recruitment and activation, resulting in accumulation of aggregated B cells in the lamina propria, B cell activation in GALTs, and an altered profile of colon antibodies.