Background/Purpose

CD22 is a sialic-acid binding co-receptor expressed primarily on B cells that has a number of functions including adhesion, regulation of B cell homeostasis and survival, and regulation of signaling through the B cell receptor (BCR) via ITIM and ITAM signaling motifs.  Mice deficient in CD22 display hyper-responsive BCR signaling, decreased numbers of marginal zone B cells and dysregulated antibody (Ab) responses to T-independent antigens.  CD22 deficiency or dysregulation also has been associated with the development of autoAbs and lupus-like disease. While primary T-dependent Ab responses are normal in CD22-deficient mice, the role of CD22 in the formation of B cell memory has not been thoroughly investigated. This study was undertaken to determine the impact of CD22 deficiency on the formation of germinal centers (GC), memory B cells and secondary recall responses.

Methods

B1-8^hi mice that harbor B cells specific for the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP) were backcrossed to CD22-deficient mice to generate Ag-specific B cells lacking CD22 for adoptive transfer studies.  Wild-type (WT) and CD22-deficient Ag-specific B cells were transferred to naïve hosts which were immunized with NP-CGG in alum.  Following immunization B cell expansion, GC differentiation, Ag presentation and memory B cell formation were monitored among Ag-binding B cells by flow cytometry.  Anti-NP serum Ab responses were monitored by ELISA. MHCII-mediated Ag presentation by GC B cell subsets was assessed by flow cytometry. WT and CD22-deficient mice were also assessed for many of the above parameters.

Results

CD22-deficient B cells mounted anti-NP Ab responses comparable to WT B cells during the early phase of the immune response (day 35).  Detailed analysis of GC B cell subsets revealed that CD22-deficient B cells failed to form a small subset of GC B cells delineated by high CXCR4 and CD38 expression.  Finally, CD22-deficient GC B cells presented similar amounts of Ag on MHCII as WT GC B cells.

Conclusion These results demonstrate that CD22 plays a critical role in the formation of memory B cells under the conditions tested, and confirm earlier reports that CD22 is not required for early T-dependent Ab responses. CXCR4^hiCD38^hi GC B cells did not develop in absence of CD22, which correlated with loss of memory B cell formation and failure to mount secondary Ab responses.  These results uncover a novel role for CD22 during T-dependent Ab responses and implicate BCR signaling regulation as a critical factor for proper formation of memory B cell precursors in the GC. They also suggest CD22-based immunotherapies could be useful for inhibiting formation of autoAg-specific memory B cells (supported by NIH grants AI44257 and AI52203)

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cd22-is-required-for-formation-of-memory-b-cell-precursors-within-germinal-centers/