Normalization of B Cell Counts and Subpopulations after Antiretroviral Therapy in Chronic HIV Disease

Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
The Journal of Infectious Diseases (Impact Factor: 6). 03/2008; 197(4):572-9. DOI: 10.1086/526789
Source: PubMed


Untreated human immunodeficiency virus (HIV) disease leads to abnormalities in all major lymphocyte populations, including CD4(+) T cells, CD8(+) T cells, and B cells. However, little is known regarding the effect of antiretroviral therapy (ART)-induced decrease in HIV viremia on B cell numbers and subpopulations.
We conducted a longitudinal study to evaluate changes in B cell numbers and subpopulations that occur during the course of 12 months of effective ART in a group of individuals with chronic HIV infection.
ART-induced decrease in HIV viremia was associated with a significant increase in B cell counts, similar to increases in CD4(+) T cell counts yet distinct from the lack of increase in CD8(+) T cells. The increase in B cell counts was accompanied by a significant decrease in the frequency of apoptosis-prone B cell subpopulations, namely mature activated and immature transitional B cells, which are overrepresented in untreated HIV disease. The increase in B cell counts was reflected by a significant increase in naive and resting memory B cells, both of which represent populations that are essential for generating adequate humoral immunity.
Normalization of B cell counts and subpopulations may help to explain the improvement in humoral immunity reported to occur after an ART-induced decrease in HIV viremia.

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Available from: Gregg Roby, Nov 24, 2015
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    • "It is currently challenged that IgM memory B cells are solely responsible for antibody formation; since isotype switched memory B cells (CD27+IgMÀ) secrete anti-polysaccharide antibodies in vitro [12]. HAART reduces polyclonal B-cell activation but has only a limited effect on the normalization of the B-cell compartment and remains to be elucidated which certain defects can be restored [13]. The loss of memory is reflected in the decline of antigen specific memory B cells post vaccination, which is not reconstituted by HAART [14] [15] [16]. "
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    • "ART, especially if initiated early in infection, is associated with recovery of total B cell counts and normalization of most B cell subpopulations, but resting memory cell recovery is incomplete [1], [3], [4]. The aging bone marrow has a reduced ability to generate naive B cells, resulting in a diminished capacity for older individuals to respond to neoantigens [6]. "
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    • "Using CD10/CD21/CD27, Moir et al. categorized peripheral blood B cells into CD10+CD27− immature/transitional, CD21loCD10− activated/mature, CD21loCD27− exhausted tissue-like memory and CD21hiCD27+ resting/memory subsets and found an expansion of the former three subsets and a contraction of the latter in HIV-1 viremic individuals [43]–[45]. As shown in Figure 3C and 3D, we found that most IL-10-producing B cells detected directly ex vivo in unstimulated PBMC from HIV-1 viremic individuals were CD10− (90.68%±3.991%) "
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