CD11b regulates antibody class switching via induction of AID
- Title
- CD11b regulates antibody class switching via induction of AID
- Author
- 이영식
- Keywords
- CD11b; B2 B cell; Antibody; Class switching; Activation-induced cytidine deaminase; NF-kappa B; SYSTEMIC-LUPUS-ERYTHEMATOSUS; PLASMA-CELL DIFFERENTIATION; B-CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; GERMINAL-CENTERS; RESPONSES; RECOMBINATION; ACTIVATION; PROLIFERATION; EXPRESSION
- Issue Date
- 2017-04
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
- Citation
- MOLECULAR IMMUNOLOGY, v. 87, Page. 47-59
- Abstract
- The integrin CD11b, which is encoded by the integrin subunit alpha M (ITGAM), is primarily expressed on the surface of innate immune cells. Genetic variations in ITGAM are among the strongest risk factors for systemic lupus erythematosus, an autoimmune disease characterized by the presence of autoantibodies. However, the regulatory function of CD11b in the antibody responses remains unclear. Here, we report the induction of CD11b in activated B2 B cells and define its unexpected role in immunoglobulin heavy chain class switch recombination (CSR). LPS-activated B cells lacking CD11b yielded fewer IgG subtypes such as IgG1 and IgG2a in vitro, and immunization-dependent CSR and affinity maturation of antibodies were severely impaired in CD11b-deficient mice. Notably, we observed the reduced expression of activation-induced cytidine deaminase (AID), an enzyme that initiates CSR and somatic hypermutation, and ectopic expression of AID was sufficient to rescue the defective CSR of CD11b-deficient B cells. LPS-induced phosphorylation of NF-kappa B p65 and I kappa B alpha was attenuated in CD11b-deficient B cells, and hyperactivation of I kappa B kinase 2 restored the defective AID expression and CSR, which implied that CD11b regulates the NF-kappa B-dependent induction of AID. Overall, our experimental evidence emphasized the function of CD11b in antibody responses and the role of CD11b as a vital regulator of CSR.
- URI
- https://www.sciencedirect.com/science/article/pii/S0161589017301049https://repository.hanyang.ac.kr/handle/20.500.11754/71959
- ISSN
- 0161-5890
- DOI
- 10.1016/j.molimm.2017.04.005
- Appears in Collections:
- COLLEGE OF SCIENCE AND CONVERGENCE TECHNOLOGY[E](과학기술융합대학) > MOLECULAR AND LIFE SCIENCE(분자생명과학과) > Articles
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