Gastrointestinal germinal center B cell depletion and reduction in IgA+plasma cells in HIV-1 infection

• DOI: 10.1101/2024.05.17.590425
• Publication Date: 2024-05-21T00:55:16Z
• Authors: Francesca Cossarini; Joan Shang; Azra Krek; Zainab Al-Taie; Ruixue Hou; Pablo Canales-Her...; Minami Tokuyama; Michael Tankelevich; Adam Tillowiz; Divya Jha; Alexandra E. Livanos; Louise Leyre; Mathieu Uzzan; Gustavo Martinez-...; Matthew D. Taylor; Keshav Sharma; Arno R Bourgonje; Michael Cruz; Giorgio Ioannou; Travis Dawson; Darwin D’Souza; Seunghee Kim-Schulze; Ahmed Akm; Judith A. Aberg; Benjamin K. Chen; Douglas S. Kwon; Sacha Gnjatic; Alexandros D. Pol...; Andrea Cerutti; Carmen Argmann; Ivan Vujkovic-Cvijin; Mayte Suarez-Fariñas; Francesca Petralia; Jeremiah J. Faith; Saurabh Mehandru
• Keywords: Male; Adult; B-Lymphocytes; Plasma Cells; HIV-1; Humans; HIV Infections; Female; Viremia; Intestinal Mucosa; Germinal Center; Immunoglobulin A

AbstractGastrointestinal (GI) B cells and plasma cells (PCs) are critical to mucosal homeostasis and the host response to HIV-1 infection. Here, high resolution mapping of human B cells and PCs sampled from the colon and ileum during both viremic and suppressed HIV-1 infection identified a reduction in germinal center (GC) B cells and follicular dendritic cells (FDCs) during HIV-1 viremia. IgA+PCs are the major cellular output of intestinal GCs and were significantly reduced during viremic HIV-1 infection. PC-associated transcriptional perturbations, including type I interferon signaling, persisted in antiretroviral therapy (ART)-treated individuals, suggesting ongoing disruption of the intestinal immune milieu during ART. GI humoral immune perturbations were associated with changes in the intestinal microbiome composition and systemic inflammation. These findings highlight a key immune defect in the GI mucosa due to HIV-1 viremia.One Sentence SummaryIntestinal germinal center B cell reduction in HIV-1 infection linked to reduced IgA+plasma cells and systemic inflammation.