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PMID: 19412542 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

CD27(-) B-cells produce class switched and somatically hyper-mutated antibodies during chronic HIV-1 infection.

PloS one ·Vol. 4 ·No. 5 ·2009-00-00 ·Pages e5427

Cagigi A, Du L, Dang LV, Grutzmeier S, Atlas A, Chiodi F, Pan-Hammarström Q, Nilsson A

Abstract

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.

MeSH Terms
B-Lymphocyte Subsets/enzymology,immunology Base Sequence CD40 Antigens/metabolism Case-Control Studies Cytidine Deaminase/metabolism DNA Primers/genetics HIV Antibodies/biosynthesis,genetics HIV Infections/enzymology,genetics,immunology HIV-1 Humans Immunoglobulin A/blood Immunoglobulin Class Switching Immunoglobulin G/blood In Vitro Techniques Lymphocyte Activation Somatic Hypermutation, Immunoglobulin Toll-Like Receptor 9/metabolism Tumor Necrosis Factor Receptor Superfamily, Member 7/metabolism
Chemicals
CD40 Antigens DNA Primers HIV Antibodies Immunoglobulin A Immunoglobulin G TLR9 protein, human Toll-Like Receptor 9 Tumor Necrosis Factor Receptor Superfamily, Member 7 AICDA (activation-induced cytidine deaminase) Cytidine Deaminase
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Cagigi Alberto
Department of Microbiology, Tumor and Cell biology, Karolinska Institutet, Stockholm, Sweden. Alberto.Cagigi@ki.se
Du Likun
Dang Linh Vu Phuong
Grutzmeier Sven
Atlas Ann
Chiodi Francesca
Pan-Hammarström Qiang
Nilsson Anna
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0005427
Email
alberto.cagigi@ki.se
Published
2009-00-00
Epub
2009-00-01
Pages
e5427
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC2671610
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.pone.0005427 PMC Full Text View journal details
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