Format

Send to

Choose Destination
Mol Immunol. 2017 Jul;87:47-59. doi: 10.1016/j.molimm.2017.04.005. Epub 2017 Apr 11.

CD11b regulates antibody class switching via induction of AID.

Author information

1
Department of Biomedical Science, College of Natural Science, Hallym University, Chuncheon 24252, Republic of Korea.
2
Center for Medical Science Research, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea.
3
Laboratory of Developmental Biology and Genomics, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea.
4
Division of Molecular and Life Science, College of Science and Technology, Hanyang University, Ansan 15588, Republic of Korea.
5
Center for Medical Science Research, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea; Department of Microbiology, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea.
6
Department of Biomedical Science, College of Natural Science, Hallym University, Chuncheon 24252, Republic of Korea. Electronic address: keunwook@hallym.ac.kr.

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-κB p65 and IκBα was attenuated in CD11b-deficient B cells, and hyperactivation of IκB kinase 2 restored the defective AID expression and CSR, which implied that CD11b regulates the NF-κB-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.

KEYWORDS:

Activation-induced cytidine deaminase; Antibody; B2B cell; CD11b; Class switching; NF-κB

PMID:
28407558
DOI:
10.1016/j.molimm.2017.04.005
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center