Studies on the freme-work of mucosal immunity by the functional analysis of novel cadherin family molecule

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We have reported a novel cadherin-family molecule, BILL-cadherin (cadherin-17), which is expressed on the B cells and its expression is spatio-temporally regulated in the course of B cell development and differentiation. BILL-cadherin is also selectively expressed in the mucosal tissues, such as intestine, nasal mucosa and lung, indicating the existence of unknown fame-work which connects B-lymhocyte system and mucosal immunity. We analysed the function of BILL-cadherin by using the mice deficient in the corresponding gene. The BILL-cadherin deficient mouse has the following phenotypes.(1)The pro-B cell population is increased about two-fold in bone marrow. (2)The size of germinal centers(GC) in spleen is significantly reduced. (3)The structure of marginal zone(MZ) is impaired. (4)The B1 population in peritoneal cavity is impaired (5)The localization of IgA^+ B cells in the intestinal lamina propria is impaired. (6)The antibody response against T-indepedndent antigen is abrogated. (7)T … More he sensitivity to Salmonella typhimurium infection is significantly desensitized. These results suggest that BILL-cadherin is involved in B-lymphocyte development and function especially in B1-subset. In addition, BILL-cadherin expressed on the intestinal epithelium is most likely involved in the mechanism of Salmonella typhmurium infection.BILL-cadherin is also expressed on the surface of pro-B cells as a molecular complex containing surrogate light chain (VpreB/λ5). The surrogate light chain is known to play the crucial roles in early B-cell development. We analysed the structural basis of the functions of surrogate light chain which might also responsible for the interaction between BILL-cadherin and the surrogate light chain. We made the series of mutant surrogate light chain components in which several amino-acids of nonimmunoglobulin domain part were substituted. The functional analyses of the mutant pre-B cell receptor indicated that the array of evolutionally conserved arginins located in nonimmunoglobulin domain of λ5 component exerts the ligand-independent, autonomous receptor activation, suggesting that the arginin-array in the nonimmunoglobulin domain is the self-crosslinking motif which allow B cells to differentiate independent of microenvironment, namely cell-autonomously. Less