Program Schedule

1610
Pervasive B cell Activation during Viremic HIV-1 Infection but Effective Responses with Appropriate Stimulation in vitro

Session: Poster Abstract Session: HIV: Basic Science
Saturday, October 11, 2014
Room: The Pennsylvania Convention Center: IDExpo Hall BC
Background: HIV-1 infection is associated with increased rates of secondary infections and decreased antibody responses to protective vaccines.  Identifying specific HIV-1-associated B cell defects may direct interventions to circumvent them.

Methods:  We studied 34 viremic HIV-1-infected adults (HIV-1+; median CD4+ T cells 276/µL; HIV-1 RNA 320,289 copies/mL) and 20 HIV-1-seronegative age-matched control subjects. We measured frequencies and activation of circulating B cell subsets and T follicular helper cells (TFH) by flow cytometry, expression of activation-induced cytidine deaminase (AID) and IL-21 by RT-qPCR, and B cell activating factor (BAFF) and IL-21 by ELISA. Cells were stimulated with surrogates for antigen (anti-IgM), cognate (anti-CD40), and soluble (IL-4) T cell factors.  Values were compared by unpaired t, paired t, and Mann Whitney tests.

Results:  At baseline, B cells from HIV-1+ adults showed perturbations in B cell subsets (increased immature transitional and IgM memory cells and decreased anergic cells) vs. controls.  Activation (CD21-) was increased across all 8 B cell subsets as were levels of B cell-activating constituents (BAFF and activated TFH cells, but not IL-21) in HIV-1+ vs. controls.   However, upon stimulation in vitro, transitions from naïve to class-switch memory cells and activation of B cells from HIV-1+ increased significantly to levels comparable to those of controls, as did levels of AID, the protein that mediates antibody class switch.

Conclusion: Viremic HIV-1 infection perturbs circulating B cell subsets and activation from the earliest developmental stages of circulating B cells.  However, with appropriate stimulation (cross-linking antigen and T cell factors), B cells can effectively activate and mature.  These data provide impetus for novel and effective vaccine development to prevent secondary infections by circumventing these early B cell defects that may limit primary protective antibody responses.

Lindsay Nicholson, MD1, Harsh Pratap, MS2, Elisabeth Bowers, PhD3, Edward M. Gardner, MD4, Timothy Wright4 and Edward Janoff, MD5, (1)Internal Medicine/Infectious Diseases, University of Colorado Denver, Aurora, CO, (2)Infectious Diseases, University of Colorado Denver, Aurora, CO, (3)University of Colorado Denver, Aurora, CO, (4)Denver Health and Hospital Authority, Denver, CO, (5)University of Colorado, Anschutz Medical Center, Aurora, CO

Disclosures:

L. Nicholson, None

H. Pratap, None

E. Bowers, None

E. M. Gardner, None

T. Wright, None

E. Janoff, None

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