title: Selective expansion of HIV-1 envelope glycoprotein-specific B cell subsets recognizing distinct structural elements following immunization.
abstract: The HIV-1 envelope glycoprotein (Env) functional spike has evolved multiple immune evasion strategies, and only a few broadly neutralizing determinants on the assembled spike are accessible to Abs. Serological studies, based upon Ab binding and neutralization activity in vitro, suggest that vaccination with current Env-based immunogens predominantly elicits Abs that bind nonneutralizing or strain-restricted neutralizing epitopes. However, the fractional specificities of the polyclonal mixture of Abs present in serum, especially those directed to conformational Env epitopes, are often difficult to determine. Furthermore, serological analyses do not provide information regarding how repeated Ag inoculation impacts the expansion and maintenance of Env-specific B cell subpopulations. Therefore, we developed a highly sensitive Env-specific B cell ELISPOT system, which allows the enumeration of Ab-secreting cells (ASC) from diverse anatomical compartments directed against different structural determinants of Env. In this study, we use this system to examine the evolution of B cell responses in mice immunized with engineered Env trimers in adjuvant. We demonstrate that the relative proportion of ASC specific for defined structural elements of Env is altered significantly by homologous booster immunizations. This results in the selective expansion of ASC directed against the variable regions of Env. We suggest that the B cell specificity and compartment analysis described in this study are important complements to serological mapping studies for the examination of B cell responses against subspecificities of a variety of immunogens.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Pia
authors.initials: P
authors.lastname: Dosenovic
authors.forename: Bimal
authors.initials: B
authors.lastname: Chakrabarti
authors.forename: Martina
authors.initials: M
authors.lastname: Soldemo
authors.forename: Iyadh
authors.initials: I
authors.lastname: Douagi
authors.forename: Mattias N E
authors.initials: MN
authors.lastname: Forsell
authors.forename: Yuxing
authors.initials: Y
authors.lastname: Li
authors.forename: Adhuna
authors.initials: A
authors.lastname: Phogat
authors.forename: Staffan
authors.initials: S
authors.lastname: Paulie
authors.forename: James
authors.initials: J
authors.lastname: Hoxie
authors.forename: Richard T
authors.initials: RT
authors.lastname: Wyatt
authors.forename: Gunilla B
authors.initials: GB
authors.lastname: Karlsson Hedestam
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D018985:Epitopes, B-Lymphocyte / Q000008:administration & dosage / Q000276:immunology*; D015483:HIV Antibodies / Q000096:biosynthesis / Q000097:blood; D007156:Immunologic Memory / Q000235:genetics; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000821:virology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D018985:Epitopes, B-Lymphocyte; D015483:HIV Antibodies; D014614:Vaccines, Synthetic; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1