Siglecs (sialic acid-binding immunoglobulin superfamily lectins) are a family of single pass, transmembrane cell surface proteins characterized by shared structural motifs and an ability to recognize sialic acids1, 2. CD22 (Siglec-2), a 140 kDa member of the Siglec family expressed by B cells3, 4, contains six C2-set domains, one V-set domain, and in its intracellular cytoplasmic tail has three immunoreceptor tyrosine-based inhibition motifs (ITIM) and one ITIM-like domain5. While murine Siglecs are not necessarily homologous to human Siglecs, CD22 is evolutionarily conserved and does have a direct human ortholog5. CD22 acts as an inhibitory B cell co-receptor that negatively regulates B cell activation, B reg cell expansion, and B cell receptor (BCR) signaling4. Upon ligation of BCR, ITIMs are phosphorylated, leading to recruitment and activation of SH2-containing phosphatases that then dephosphorylate signaling molecules activated by BCR ligation4. Additionally, CD22 regulates B cell response to inflammation and is a master regulator of microglial phagocytosis in the aging brain5. Evidence in mouse models suggests CD22 contributes to the pathogenesis of autoimmune diseases3. Loss of CD22 leads to hyperactivation of B cells5. CD22 mouse knockouts are defective in B cell development but do not develop lupus-like disease4. To generate MB22-11, CD22 knockout mice were immunized with mouse CD22 cDNA-transfected baby hamster kidney cells6. Spleen cells were fused with NS-1 myeloma cells, and hybridomas producing antibody specifically reactive with CD22-transfected mouse L cells were selected and purified. MB22-11 was isotyped as IgG2c due to its C57BL/6 origin; however, both IgG2a and IgG2c specific reagents have significant reactivity against MB22-11. In vitro, MB22-11 inhibits CD22-mediated adhesion by 90% and completely blocks CD22-Fc binding to T and B cells6. In vivo, MB22-11 significantly reduces peripheral blood, lymph node, and marginal zone B cell numbers6, 7. Additionally, in mice injected with MB22-11, blood, spleen, and lymph node B cell turnover is higher relative to injection with non-blocking monoclonal antibodies, and B cell surface expression of CD22 is reduced to nearly undetectable levels6.