Why are the "antibody factories" in men and women not the same? The Bohai team today published a paper in Nature revealing important mechanisms.

▎ academic longitude / report ▎ B lymphocytes in the immune system play an important role in resisting pathogens. When they discover an intruder, they produce antibodies against the enemy.however, this important ability is not "gender equality".today, a research team led by Professor Qi Hai of Tsinghua University published a paper online in nature, a top academic journal, to help us understand why there are differences in humoral immune response between men and women, and to reveal the cellular mechanism behind this phenomenon.this work will also contribute to the development of new drugs, enhance the effectiveness of vaccination, and treat intractable autoimmune diseases.the immune response mediated by antibodies is called "humoral immune response".when we are young, we use our own protective antibodies to prevent diseases.although healthy people have this ability, the humoral immune responses of men and women are different: women usually produce more antibodies than men to protect themselves.this protective ability can sometimes be more than enough, leading to the immune system attacking the normal organs and tissues of the human body.for example, a research progress on lupus erythematosus was introduced not long ago.lupus erythematosus is an autoimmune disease with strong B cell response, and the possibility of lupus erythematosus in women is significantly higher than that in men.} the corresponding author of this study, Professor Qi Hai of Tsinghua University, is the winner of the "Scholar Award" of 2017 Yao Ming Kant's Life Chemistry Research Award (photo source: Yao Ming Kant). There are also gender differences in humoral immune response in other mammals.so, in order to find out the underlying reasons, Qi Hai's team first compared the B-cell development process of female mice and male mice.before growing into "antibody factory", B cells will migrate after being activated by antigen and form germinal centers in lymphoid follicles.the researchers found that male B cells did not appear to be as well positioned as female B cells during this process.after the same period of time, female B cells occupied more central position in the lymphoid follicles, while many male B cells were located at the edge.further analysis showed that a gene located on the X chromosome could inhibit the formation of germinal center of male mouse B cells, which may be the key to the gender difference! The gpr174 expressing B cells (green) are closer to the edge of follicles (blue) and T cells (red) (photo source: reference [1]). Gpr174, a protein encoded by this gene, is a receptor expressed in B cells, which drives B cells to the edge of follicles like a guide.when the researchers removed gpr174 from male B cells, it was found that they became more easily located in the center, and correspondingly formed more germinal centers. however, this receptor did not affect the B cells of female mice. in this work, the team also identified the molecule CCL21 of gpr174 through mass spectrometry analysis and biochemical experiments, and verified that testosterone can affect the activation of gpr174 protein, thus gradually clarifying the fine regulation mode of male B cells in the process of development and maturation. conversely, in an autoimmune disease model with B-cell overreaction, the researchers verified that the response of gpr174 to CCL21 was different between male and female, which was also a reason why the humoral immune response of male was weaker than that of female. In the mouse model of human multiple sclerosis, the deletion of gpr174 did not affect the female mice (red), and the symptoms of male mice (blue) increased (photo source: reference [1]). Although the function of gpr174 in human body needs to be further verified, however, the authors mentioned at the end of the paper that gpr174 signal transduction was selectively targeted or inhibited Cheng, may help improve the effectiveness of the vaccine, especially if it fails to respond well in some men. we congratulate Professor Qi Hai's research team on this achievement, and we look forward to the follow-up research progress of scientists to help us better understand the problems related to the immune system, which can benefit both men and women in the end. References: [1] ruozhu Zhao et al. (2019) a gpr174 – CCL21 module impairments seminal morphology to human immunity. Nature Doi:10.1038/s41586-019-1873-0