Nature. In a major new discovery, Tsinghua University's Bohai team has revealed a mechanism by which men's immunity is lower than women's.

The sensitivity of the humoral immune response to immunity and infection and to antibody mediated autoimmunity was low. However, the underlying mechanism of this dimorphism has not been well understood.on December 25, 2019, Qi Hai team of Tsinghua University published a research paper entitled "a gpr174 – CCL21 module imparts semantic to human immunity" online in nature. The study identified gpr174 as the receptor of CCL21, and revealed that its chemotaxis on activated B cells was the mechanism of humoral response and autoimmune dimorphism.the differential coupling of testosterone and G α I protein is the basis of the different effects of gpr174 on the migration of male and female B cells to CCL21.the sensitivity of humoral immune response to immunity and infection and to antibody mediated autoimmunity is low in men. However, the underlying mechanism of this dimorphism has not been well understood.here, the researchers showed an inherent difference between the B cells that produce germinal centers in male and female mice.this study found that antigen activated male B cells could not locate in the germinal center of follicular center of secondary lymphoid organs as effectively as female B cells, in which germinal centers usually developed.gpr174 regulates B-cell localization and inhibits the formation of germinal centers in male (but not female) mice. In addition, gpr174 is a G protein coupled receptor encoded by X chromosome, which can inhibit the formation of germinal centers in male mice (not female mice).this effect is inherent in B cells and is related to the location of gpr174 enhanced B cells towards the T-B cell boundary of follicles, and to the dispersion of male rather than female B cells from s1pr2 driven follicles.gpr174 reduces EAE sensitivity and autoantibody titer of male mice. CCL21 can be identified as gpr174 ligand by biochemical grading of conditioned medium for gpr174 dependent B cell migration.in response to CCL21, gpr174 triggered calcium flux and preferentially induced male B cell migration.gpr174 is also associated with more g α I protein than female B cells.the male B cells of testis removed mice showed impaired gpr174 mediated migration to CCL21, which could be remedied by testosterone therapy.testosterone treated female B cells showed similar gpr174 – g α I Association and gpr174 mediated migration.the deletion of gpr174 from male B cells leads to more effective localization of gpr174 in the center of follicles, forming more germinal centers, and increasing the sensitivity to B-cell-dependent autoimmune encephalomyelitis.by identifying gpr174 as a receptor for CCL21 and demonstrating its sex dependent control of B cell localization and participation in germinal center, this study reveals a mechanism by which B cell physiology can be fine tuned to endow humoral immune dimorphism.reference message: