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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    • "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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    ABSTRACT: Older HIV infected subjects were previously found to have significant B cell expansion during initial antiretroviral therapy in a prospective age-differentiated cohort of older and younger (≥45 vs. ≤30 years) HIV-infected subjects initiating antiretroviral therapy (ART) through the AIDS Clinical Trials Group. Here to further describe this expansion, using a subset of subjects from the same cohort, we characterized B cell phenotypes at baseline and after 192 weeks of ART in both older and younger HIV-infected groups and compared them to uninfected age-matched controls. We also examined whether phenotypes at baseline associated with response to tetanus and hepatitis A vaccine at 12 weeks. Forty six subjects were analyzed in the HIV infected group (21 older, 25 younger) and 30 in the control group (15 per age group). We observed naïve B cells to normalize in younger subjects after 192 weeks of ART, while in older subjects naïve B cells increased to greater levels than those of controls (p = 0.045). Absolute resting memory (RM) cell count was significantly lower in the older HIV infected group at baseline compared to controls and numbers normalized after 192 weeks of ART (p<0.001). Baseline RM cell count positively correlated with week 12 increase in antibody to tetanus vaccine among both younger and older HIV-infected subjects combined (p = 0.01), but not in controls. The age-associated naïve B cell expansion is a novel finding and we discuss several possible explanations for this observation. Relationship between RM cells at baseline and tetanus responses may lead to insights about the effects of HIV infection on B cell memory function and vaccine responses.
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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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