Rad9 is required for B cell proliferation and immunoglobulin class switch recombination.
B cell maturation and B cell-mediated antibody response require programmed DNA modifications such as the V(D)J recombination, the immunoglobulin (Ig) class switch recombination, and the somatic hypermutation to generate functional Igs. Many protein factors involved in DNA damage repair have been shown to be critical for the maturation and activation of B cells. Rad9 plays an important role in both DNA repair and cell cycle checkpoint control. However, its role in Ig generation has not been reported. In this study, we generated a conditional knock-out mouse line in which Rad9 is deleted specifically in B cells and investigated the function of Rad9 in B cells. The Rad9(-/-) B cells isolated from the conditional knock-out mice displayed impaired growth response and enhanced DNA lesions. Impaired Ig production in response to immunization in Rad9(-/-) mice was also detected. In addition, the Ig class switch recombination is deficient in Rad9(-/-) B cells. Taken together, Rad9 plays dual roles in generating functional antibodies and in maintaining the integrity of the whole genome in B cells.
An
Lili
L
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Wang
Yulan
Y
Liu
Yuheng
Y
Yang
Xiao
X
Liu
Chunchun
C
Hu
Zhishang
Z
He
Wei
W
Song
Wenxia
W
Hang
Haiying
H
D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015153:Blotting, Western; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015321:Gene Rearrangement; D006241:Haptens; D006433:Hemocyanins / Q000276:immunology; D007114:Immunization; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D015847:Interleukin-4 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic
D018941:Antigens, CD19; D018797:Cell Cycle Proteins; D006241:Haptens; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; C054401:trinitrophenyl keyhole limpet hemocyanin; C069930:rad9 protein; D015847:Interleukin-4; D006433:Hemocyanins