| First Author | Meyer SJ | Year | 2021 |
| Journal | J Immunol | Volume | 207 |
| Issue | 4 | Pages | 1018-1032 |
| PubMed ID | 34330755 | Mgi Jnum | J:318700 |
| Mgi Id | MGI:6845009 | Doi | 10.4049/jimmunol.2100132 |
| Citation | Meyer SJ, et al. (2021) CD22 Controls Germinal Center B Cell Receptor Signaling, Which Influences Plasma Cell and Memory B Cell Output. J Immunol 207(4):1018-1032 |
| abstractText | 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 CD22(-/-) 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 CD22(-/-) GC B cells was responsible for the disadvantage, also leading to a lower GC output in plasma cells and memory B cells. CD22(-/-) 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. |
