Melanie Wickert

Cytokine production of B cells in patients with variable immune deficiency

B cell subpopulations of a healthy donor (left) and a CVID patient showing CD21low B cells (right)

B cell subpopulations of a healthy donor (left) and a CVID patient showing CD21low B cells (right)

For my Bachelor’s project, I investigated the Cytokine production of B cells, especially of CD21low B cells, in a subgroup of patients with common variable immune deficiency (CVID). CVID is the most common primary immune deficiency in adults, and is characterised by recurrent infections, low antibody levels in at least two immunoglobulin types, and immune dysregulation. Some CVID patients have an extraordinary expansion of an unusual B cell population characterised by the low expression of CD21. CD21low B cells occur in the peripheral blood as well as inflammatory tissue. They are polyclonal unmutated IgM(+)IgD(+) B cells, which differ in their distinct gene expression profile from conventional naive B cells. This subpopulation of B cells is nonexistent in healthy or other CVID patients and the function of these cells is unclear.

For this, the peripheral blood b cell populations of healthy donors were investigated for the cytokine production, looking at pro-inflammatory cytokines IL-6, TNF-α and IL-8 as well as the anti-inflammatory cytokine IL-10. I showed that memory B cells produce more cytokines than naive B cells. Comparing now naive B cells of the healthy donors, with B cells of CVID patients with and without CD21low B cells, it could be shown that it is not the CD21low B cells that produce more pro-inflammatory cytokines, but the CD21pos B cells. In fact, the CD21low B cells seem to produce more IL-10 than naive B cells. Noticeable was the spontaneous production of IL-8 and the increased recruitment of granulocytes in the inflammatory tissue. After three days of stimulation a decreasing production of IL-6 in both the CD21low B cells and the plasma cells could be shown, which points to a problem in the plasma cell differentiation and therefore a potential decrease in activation of these cells.

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