Immunogenetic analysis of the resistance to infectious diseases

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Both CD22 and CD72 are B lymphocyte membrane molecules that negatively regulate signaling thorough B cell antigen receptor. Both CD22 and CD72 genes are polymorphic. To elucidate whether polymorphisms of these genes are associated with resistance to acute infection, we examined haplotypes of both CD22 and CD72 in SARS patients in China and individuals who were close contact with SARS patients but did not develop SARS. A CD72 haplotype was tend to be increased in patients with severe symptoms although the increase was not significant because of the limited sample numbers. Next, we examined the functional difference of different CD72 haplotypes. The human CD72 gene generates two distinct splicing isoforms, i.e., full length CD72 and CD72 lacking exon 8 (CD72 Δ ex8). We demonstrated that the level of CD72 Δ ex8 but not full length CD72 depends on CD72 haoplotypes. Moreover, CD72 Δ ex8 is accumulated in the endoplastic reticulum (ER), and augments ER stress and apoptosis mediated by ER stress. These results indicate that CD72 polymorphism regulates expression of CD72 Δ ex8 that regulates B lymphocyte apoptosis mediated by ER stress, thereby regulating infection immunity.