Characterizing the primary B cell antibody response to HIV (53.18)

Abstract

Abstract Most individuals infected with the human immunodeficiency virus (HIV) make neutralizing antibodies (nAbs) to the virus, but this response is delayed and consequently not protective. Some nAbs that have been characterized are described as polyreactive and slightly autoreactive, two attributes of Abs produced by marginal zone (MZ) B cells. Thus, B cells capable of producing nAbs early in infection may not participate, possibly because of tolerance mechanisms. To directly examine the components of the primary Ab response to the HIV envelope protein gp120, we use a mouse model and HIV viral-like particles (VLPs). Our studies focus on the quantity and quality of the anti-HIV responses from different B cell subsets. We have found that naïve follicular (FO) and MZ B cells are both capable of producing anti-gp120 IgM in culture. Additionally, we have examined the VDJ rearrangements of gp120-reactive Abs from different populations in both the naïve and VLP-challenged repertoire. So far, it seems that there may be a preferred VDJ recombination event that is over-represented in the MZ B cell compartment. This VDJ rearrangement has not yet been found in responding cells of VLP-immunized mice, indicating that MZ B cells may not be participating in the VLP response. Abs from these subsets are being further characterized with HIV-neutralization studies. It is expected that the results from these experiments will prove informative for the development of a protective HIV vaccine.