CD27(-) B-cells produce class switched and somatically hyper-mutated antibodies during chronic HIV-1 infection.
Class switch recombination and somatic hypermutation occur in mature B-cells in response to antigen stimulation. These processes are crucial for the generation of functional antibodies. During HIV-1 infection, loss of memory B-cells, together with an altered differentiation of naïve B-cells result in production of low quality antibodies, which may be due to impaired immunoglobulin affinity maturation. In the current study, we evaluated the effect of HIV-1 infection on class switch recombination and somatic hypermutation by studying the expression of activation-induced cytidine deaminase (AID) in peripheral B-cells from a cohort of chronically HIV-1 infected patients as compared to a group of healthy controls. In parallel, we also characterized the phenotype of B-cells and their ability to produce immunoglobulins in vitro. Cells from HIV-1 infected patients showed higher baseline levels of AID expression and increased IgA production measured ex-vivo and upon CD40 and TLR9 stimulation in vitro. Moreover, the percentage of CD27(-)IgA+ and CD27(-)IgG+ B-cells in blood was significantly increased in HIV-1 infected patients as compared to controls. Interestingly, our results showed a significantly increased number of somatic hypermutations in the VH genes in CD27(-) cells from patients. Taken together, these results show that during HIV-1 infection, CD27(-) B-cells can also produce class switched and somatically hypermutated antibodies. Our data add important information for the understanding of the mechanisms underlying the loss of specific antibody production observed during HIV-1 infection.
Cagigi
Alberto
A
Department of Microbiology, Tumor and Cell biology, Karolinska Institutet, Stockholm, Sweden. Alberto.Cagigi@ki.se
Du
Likun
L
Dang
Linh Vu Phuong
LV
Grutzmeier
Sven
S
Atlas
Ann
A
Chiodi
Francesca
F
Pan-Hammarström
Qiang
Q
Nilsson
Anna
A
D016175:B-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology*; D001483:Base Sequence; D019013:CD40 Antigens / Q000378:metabolism; D016022:Case-Control Studies; D003564:Cytidine Deaminase / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D015483:HIV Antibodies / Q000096:biosynthesis* / Q000235:genetics*; D015658:HIV Infections / Q000201:enzymology / Q000235:genetics* / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000097:blood; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D027041:Somatic Hypermutation, Immunoglobulin; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D019013:CD40 Antigens; D017931:DNA Primers; D015483:HIV Antibodies; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase