Germinal centers (GC) are established in the context of a T-cell-dependent immune response and orchestrate antibody affinity maturation and B cell differentiation. Compared to naïve B cells, GC B cells show attenuated B-cell-receptor (BCR) signaling in response to antigen stimulation and display rewired BCR signaling. GC B cells also show changes in surface glycosylation, including changes in sialic acids, like Neu5Ac expression instead of Neu5Gc.
CD22 is a protein of the Siglec family and an important inhibitor on B cells. On naïve B cells, CD22 binds to α-2,6-sialic acid ligands (Neu5Gc) in cis and forms clusters of CD22 homo-oligomers, distinct from the BCR. While a deletion of CD22 leads to B cell hyperreactivity with elevated BCR Ca2+ response, a reduction of CD22 cis-ligand binding leads to higher CD22-BCR association and reduced BCR signaling. As GC B cells only express Neu5Ac (20x weaker CD22 binding), a loss of CD22 cis-ligand binding in the GC could play a causative role in the reduction of BCR signaling. Indeed, Ca2+ signaling of CD22-/- GC B cells is increased. This elevated BCR response leads to impaired GC B cell numbers during an ongoing GC reaction. Our hypothesis is that BCR signaling in GC B cells needs to be tightly controlled and that changes in the signaling strength affect B cell metabolism and the quality of the immune response.