Author : Lindsey Pujanauski
Publisher :
ISBN 13 :
Total Pages : 148 pages
Book Rating : 4.:/5 (955 download)
Book Synopsis B Cell Subset Contributions to the Primary HIV Antibody Response by : Lindsey Pujanauski
Download or read book B Cell Subset Contributions to the Primary HIV Antibody Response written by Lindsey Pujanauski and published by . This book was released on 2013 with total page 148 pages. Available in PDF, EPUB and Kindle. Book excerpt: Despite global efforts, a preventative HIV vaccine remains elusive. The correlates of protection against HIV infection are as yet undefined, but clues can be drawn from potent antibodies able to neutralize diverse HIV strains. A series of potent broadly-neutralizing HIV antibodies have recently been isolated from B cells of HIV-infected individuals. VRC01 represents a subset of these antibodies that mediate neutralization with a restricted set of IGHV genes. The memory B cells that expressed these antibodies were isolated years after infection. Therefore, the B cell subpopulation from which they originated and the extent of participation in the initial HIV antibody response, if any, is unclear. Here, we evaluated the frequency of anti-gp120 B cells in follicular (FO) and marginal zone (MZ) B cell compartments of naïve wild type mice and the comparable human populations in uninfected individuals. We find that in HIV-unexposed humans and mice, the majority of gp120-reactive B cells are of naïve or FO phenotype, respectively. In a vaccine setting using HIV viral-like particles in alum, FO B cells appear to be the dominant anti-g120 responders. Unchallenged murine FO B cells express a diverse antibody repertoire to recognize gp120. In contrast, mouse MZ B cells recognize gp120 less frequently but preferentially use IGHV1-53 to encode gp120-specific antibodies. These germline antibodies are polyreactive and unable to neutralize HIV. Notably, IGHV1-53 shows high identity to human IGHV1-2*02, which has repeatedly been found to encode broadly-neutralizing mutated HIV antibodies, such as VRC01. Finally, we show that human MZ-like B cells express IGHV1-2*02 and that IGHV1-53 expression is enriched in mouse MZ B cells. These data suggest that efforts towards an HIV vaccine might consider eliciting protective HIV antibody responses selectively from alternative B cell populations harboring IGHV gene segments that are capable of producing protective antibodies.
