Moysi Eirini, Sharma Ashish A, O'Dell Sijy, Georgakis Spiros, Del Rio Estrada Perla Mariana, Torres-Ruiz Fernanda, Navarro Mauricio González, Villalobos Yara Andrea Luna, Rios Santiago Avila, Reyes-Teran Gustavo, Beddall Margaret H, Ko Sung-Hee, Belinky Frida, Orfanakis Michail, de Leval Laurence, Enriquez Ana B, Buckner Clarisa M, Moir Susan, Doria-Rose Nicole, Boritz Eli, Mascola John R, Sekaly Rafick-Pierre, Koup Richard A, Petrovas Constantinos
Tissue Analysis Core, Immunology Laboratory, Vaccine Research Center, NIAID, NIH, Bethesda, MD, USA.
Pathology Advanced Translational Research Unit, Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.
bioRxiv. 2024 Aug 3:2024.07.31.605954. doi: 10.1101/2024.07.31.605954.
A subset of people living with HIV (PLWH) can produce broadly neutralizing antibodies (bNAbs) against HIV, but the lymph node (LN) dynamics that promote the generation of these antibodies are poorly understood. Here, we explored LN-associated histological, immunological, and virological mechanisms of bNAb generation in a cohort of anti-retroviral therapy (ART)-naïve PLWH. We found that participants who produce bNAbs, termed neutralizers, have a superior LN-associated B cell follicle architecture compared with PLWH who do not. The latter was associated with a significantly higher prevalence of Bcl-6 follicular helper CD4 T cells (TFH), expressing a molecular program that favors their differentiation and stemness, and significantly reduced IL-10 follicular suppressor CD4 T cells. Furthermore, our data reveal possible molecular targets mediating TFH- B cell interactions in neutralizers. Together, we identify cellular and molecular mechanisms that contribute to the development of bNAbs in PLWH.
Front Immunol. 2019-7-2
Annu Rev Immunol. 2022-4-26
Proc Natl Acad Sci U S A. 2021-5-4
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