A Molecular Mechanism of High IgM Immunodeficiency

In the adaptive immune system, the diversity of antibody molecules produced by B lymphocytes is the key effector molecule in mediating humoral immunity.

Clinically, mutations in AID protein have been found to be closely related to immunodeficiency disease type 2 hyper-IgM syndrome, and these mutations are mostly ^recessive inheritance

On April 26, 2022, researcher Hu Jiazhi's research group from the School of Life Sciences of Peking University and Peking University-Tsinghua Life Science Joint Center cooperated with researcher Meng Feilong's research group of the Center for Excellence in Molecular and Cell Science (Institute of Biochemistry and Cell Biology), Chinese Academy of Sciences.

Figure 1.

By means of endogenous protein tagging and CRISPR-Sirius targeting, the researchers found that AID ^DCs existed in the form of aggregates in B lymphocytes, and the aggregates were sequestered outside the IgH region and lost the targeting antibody gene.

Figure 2.

Through intracellular co-expression experiments, the researchers found that AID ^DC aggregates could specifically capture free wild-type AID in the nucleus into the aggregates (Fig.

Figure 3.

Hu Jiazhi and Meng Feilong are the co-corresponding authors of the article