Independent expansion of epitope-specific plasma cell responses upon HIV-1 envelope glycoprotein immunization

• Published in: The Journal of immunology (1950) 2013-07, Vol.191 (1), p.44-51
• Main Authors: Forsell, Mattias N E, Soldemo, Martina, Dosenovic, Pia, Wyatt, Richard T, Karlsson, Mikael C I, Karlsson Hedestam, Gunilla B
• Format: Article
• Language: English
• Subjects: AIDS Vaccines - administration & dosage; AIDS Vaccines - chemistry; AIDS Vaccines - immunology; Animals; B-Lymphocyte Subsets - cytology; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - secretion; Cell Differentiation - immunology; env Gene Products, Human Immunodeficiency Virus - administration & dosage; env Gene Products, Human Immunodeficiency Virus - immunology; Epitopes, B-Lymphocyte - biosynthesis; Epitopes, B-Lymphocyte - immunology; Epitopes, B-Lymphocyte - metabolism; Female; HIV Envelope Protein gp120 - administration & dosage; HIV Envelope Protein gp120 - immunology; Human immunodeficiency virus 1; Humans; Immunization, Secondary; Immunoglobulin G - biosynthesis; Immunoglobulin M - biosynthesis; Lymphocyte Activation - immunology; Male; Mice; Mice, Inbred BALB C; Plasma Cells - cytology; Plasma Cells - immunology; Plasma Cells - secretion; Protein Subunits - administration & dosage; Protein Subunits - chemistry; Protein Subunits - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1203087

Abs that bind the functional envelope glycoprotein (Env) spike are considered critical for a broadly effective prophylactic HIV-1 vaccine. The difficulty in eliciting such Abs by vaccination is partially attributed to the immunodominance of hydrophilic, surface-exposed variable protein regions of Env. However, little is known about the potential for competition between B cells that recognize distinct and distal epitopes on Env during protein subunit vaccination. In this study, we address this basic question at the level of Ab-secreting cells and serum IgG using a pair of isogenic soluble Env trimers, designated wildtype and gV3, which differ only in their potential to activate B cell responses against the highly immunogenic V3 region of Env. Immunization of mice with gV3 resulted in a markedly lower Ag-specific response compared with that induced by wildtype Env and could be explained by a loss of V3-directed reactivities. There was no redistribution of the response to other regions of Env in gV3-inoculated mice, suggesting that the epitope-specific Ab-secreting cell responses measured after boost are independently regulated rather than dictated by direct or indirect competition between B cells recognizing different structural elements of Env. This information is relevant for ongoing efforts in Env immunogen design to focus responses on conserved neutralizing determinants and for our general understanding of B cell responses to large-protein Ags that display numerous B cell epitopes.