Cd22 controls germinal center b cell receptor signaling, which influences plasma cell and memory b cell output

Meyer SJ, Steffensen M, Acs A, Weisenburger T, Wadewitz C, Winkler T, Nitschke L (2021)


Publication Type: Journal article

Publication year: 2021

Journal

Book Volume: 207

Pages Range: 1018-1032

Journal Issue: 4

DOI: 10.4049/jimmunol.2100132

Abstract

Germinal center reactions are established during a thymus-dependent immune response. Germinal center (GC) B cells are rapidly proliferating and undergo somatic hypermutation in Ab genes. This results in the production of high-affinity Abs and establishment of long-lived memory cells. GC B cells show lower BCR-induced signaling when compared with naive B cells, but the functional relevance is not clear. CD22 is a member of the Siglec family and functions as an inhibitory coreceptor on B cells. Interestingly, GC B cells downregulate sialic acid forms that serve as high-affinity ligands for CD22, indicating a role for CD22 ligand binding during GC responses. We studied the role of CD22 in the GC with mixed bone marrow chimeric mice and found a disadvantage of CD222/2 GC B cells during the GC reaction. Mechanistic investigations ruled out defects in dark zone/light zone distribution and affinity maturation. Rather, an increased rate of apoptosis in CD222/2 GC B cells was responsible for the disadvantage, also leading to a lower GC output in plasma cells and memory B cells. CD222/2 GC B cells showed a clearly increased calcium response upon BCR stimulation, which was almost absent in wild-type GC B cells. We conclude that the differential expression of the low-affinity cis CD22 ligands in the GC normally results in a strong attenuation of BCR signaling in GC B cells, probably due to higher CD22-BCR interactions. Therefore, attenuation of BCR signaling by CD22 is involved in GC output and B cell fate.

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How to cite

APA:

Meyer, S.J., Steffensen, M., Acs, A., Weisenburger, T., Wadewitz, C., Winkler, T., & Nitschke, L. (2021). Cd22 controls germinal center b cell receptor signaling, which influences plasma cell and memory b cell output. Journal of Immunology, 207(4), 1018-1032. https://dx.doi.org/10.4049/jimmunol.2100132

MLA:

Meyer, Sarah Johanna, et al. "Cd22 controls germinal center b cell receptor signaling, which influences plasma cell and memory b cell output." Journal of Immunology 207.4 (2021): 1018-1032.

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