The role of Siglec proteins in B cell activation and autoimmunity (04)

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B cells express CD22 and Siglec-G as inhibitory receptors on the cell surface, which can suppress B cell responses. The E3 ubiquitin ligase cullin 3 was identified as a CD22-interacting protein, which regulates the CD22 surface expression on B cells. The role of CD22 and Siglec-G in spontaneous autoimmunity was studied in mice with mutations in both genes. The role of Siglec-G in B cell chronic lymphocytic leukemia (B-CLL) was analysed in a B-CLL mouse model. B-CLL developed much earlier, when the mice were deficient for Siglec-G. This will be followed up in the third funding period. The role of CD22 in germinal centre responses will also be examined, as preliminary results have shown a competitive disadvantage of CD22 KO GC B cells.