pmc logo imageJournal ListSearchpmc logo image
Logo of plosonePLoS OneView this ArticleSubmit to PLoSGet E-mail AlertsContact UsPublic Library of Science (PLoS)
Journal List > PLoS ONE > v.4(5); 2009
>Abstract
Full Text
PDF (260K)
Contents
Archive

PubMed articles by:
Cagigi, A.
Du, L.
Dang, L.
Nilsson, A.
PLoS ONE. 2009; 4(5): e5427.
Published online 2009 May 1. doi: 10.1371/journal.pone.0005427.
PMCID: PMC2671610
Copyright Cagigi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
CD27− B-Cells Produce Class Switched and Somatically Hyper-Mutated Antibodies during Chronic HIV-1 Infection
Alberto Cagigi,1* Likun Du,2 Linh Vu Phuong Dang,1 Sven Grutzmeier,3 Ann Atlas,4 Francesca Chiodi,1 Qiang Pan-Hammarström,#2 and Anna Nilsson#1,5
1Department of Microbiology, Tumor and Cell biology, Karolinska Institutet, Stockholm, Sweden
2Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden
3Gay Men's Health Clinic, The South Hospital, Stockholm, Sweden
4Department of Medicine Solna, Infectious Diseases Unit, Karolinska University Hospital, Stockholm, Sweden
5Department of Women and Child Health, Karolinska Institutet, Stockholm, Sweden
Derya Unutmaz, Editor
New York University School of Medicine, United States of America
#Contributed equally.
* E-mail: Alberto.Cagigi/at/ki.se
Conceived and designed the experiments: AC FC QPH AN. Performed the experiments: AC LD LVPD. Analyzed the data: AC FC QPH AN. Contributed reagents/materials/analysis tools: AC SG AA. Wrote the paper: AC FC QPH AN.
Received January 8, 2009; Accepted April 9, 2009.
 
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.
Articles from PLoS ONE are provided here courtesy of
Public Library of Science