Human IgMhiCD300a+ B Cells Are Circulating Marginal Zone Memory B Cells That Respond to Pneumococcal Polysaccharides and Their Frequency Is Decreased in People Living with HIV

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).CD300a is differentially expressed among B cell subsets, although its expression in immunoglobulin (Ig)M+ B cells is not well known. We identified a B cell subset expressing CD300a and high levels of IgM (IgMhiCD300a+). The results showed that IgMhiCD300a+ B cells were CD10−CD27+CD25+IgDloCD21hiCD23−CD38loCD1chi, suggesting that they are circulating marginal zone (MZ) IgM memory B cells. Regarding the immunoglobulin repertoire, IgMhiCD300a+ B cells exhibited a higher mutation rate and usage of the IgH-VDJ genes than the IgM+CD300a− counterpart. Moreover, the shorter complementarity-determining region 3 (CDR3) amino acid (AA) length from IgMhiCD300a+ B cells together with the predicted antigen experience repertoire indicates that this B cell subset has a memory phenotype. IgM memory B cells are important in T cell-independent responses. Accordingly, we demonstrate that this particular subset secretes higher amounts of IgM after stimulation with pneumococcal polysaccharides or a toll-like receptor 9 (TLR9) agonist than IgM+CD300a− cells. Finally, the frequency of IgMhiCD300a+ B cells was lower in people living with HIV-1 (PLWH) and it was inversely correlated with the years with HIV infection. Altogether, these data help to identify a memory B cell subset that contributes to T cell-independent responses to pneumococcal infections and may explain the increase in severe pneumococcal infections and the impaired responses to pneumococcal vaccination in PLWH.This work was supported by the following grants to F.B.: Agencia Estatal de Investigación (PID2019-109583RB-I00/AEI/10.13039/501100011033) and Gilead Fellowship Program (GLD15/00303). A grant to B.d.A.: Agencia Estatal de Investigación-ISCIII (PI22CIII/00030). J.V. and I.T. are recipients of a predoctoral contract funded by the Department of Education, Basque Government (PRE_2018_2_0242 and PRE_2021_2_0215). A.O and I.T. are recipients of a fellowship from the Jesús de Gangoiti Barrera Foundation (FJGB18/002 and FJGB19/002). L.A. is an Ikerbasque Research Fellow, Ikerbasque, Basque Foundation for Science. F.B. is an Ikerbasque Research Professor, Ikerbasque, Basque Foundation for Science. We want to particularly acknowledge the patients in this study for their participation, to the HIV BioBank and the collaborating centres for the generous gifts of the clinical samples used in this study. The HIV BioBank is supported by Instituto de Salud Carlos III (PT20/00138) and Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN (CB22/01/00041). CoRIS cohort is supported by CIBER—Consorcio Centro de Investigación Biomédica en Red—(CB21/13/00091), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea—NextGenerationEU. This study would not have been possible without the collaboration of all patients, medical and nursing staff and data managers who have taken part in the Project. CoRIS cohort is supported by CIBER—Consorcio Centro de Investigación Biomédica en Red—(CB21/13/00091), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea—NextGenerationEU.Peer reviewe

Polyfunctional HIV-1 specific response by CD8+ T lymphocytes expressing high levels of CD300a

CD300a receptor is found on different CD8+ T cell subsets and its expression has been associated to a more cytotoxic molecular signature. CD300a has an important role in some viral infections and its expression levels are known to be modulated by human immunodeficiency virus (HIV)−1 infection on several cell types. The main objective of this work was to investigate CD300a expression and its regulation during HIV-1 specific CD8+ T cell responses. CD300a receptor expression was analysed by multiparametric flow cytometry on CD8+ T lymphocytes from HIV negative donors, naive HIV-1+ individuals and HIV-1+ subjects under suppressive combined antiretroviral therapy (cART). HIV-1 specific CD8+ T cell response was studied by stimulating cells with HIV-1 derived peptides or with a Gag HIV-1 peptide. Our results showed that HIV-1 specific CD8+ T cells expressing higher levels of CD300a were more polyfunctional showing an increased degranulation and cytokine production. Moreover, we observed an up-regulation of CD300a expression after Gag HIV-1 peptide stimulation. Finally, our results demonstrated an inverse correlation between CD300a expression on CD8+ T lymphocytes and HIV disease progression markers. In conclusion, CD300a expression is associated to a better and more polyfunctional HIV-1 specific CD8+ T cell response.This study was supported by a grant from “Plan Estatal de I+ D+ I 2013–2016, ISCIII-Subdirección de Evaluación y Fomento de la Investigación-Fondo Europeo de Desarrollo Regional (FEDER) (Grant PI13/00889)” and Marie Curie Actions, Career Integration Grant, European Commission (Grant CIG 631674). Joana Vitallé and Iñigo Terrén are recipients of a predoctoral contract funded by the Department of Education, Basque Government (PRE_2017_2_0242 and PRE_2018_1_0032). Joana Vitallé and Iñigo Terrén are recipients of a fellowship from the Jesús de Gangoiti Barrera Foundation (FJGB15/008 and FJGB17/003). Laura Tarancón-Díez was supported by Instituto de Salud Carlos III, PFIS (FI00/00431). Olatz Zenarruzabeitia is recipient of a postdoctoral contract funded by “Instituto de Salud Carlos III-Contratos Sara Borrell 2017 (CD17/0128)” and the European Social Fund (ESF)-The ESF invests in your future. Ezequiel Ruiz-Mateos is supported by Programa Nicolás Monardes, C0032-2017, Consejería de Salud y Bienestar Social, Junta de Andalucía. Francisco Borrego is an Ikerbasque Research Professor, Ikerbasque, Basque Foundation for Science

Altered expression of CD300a inhibitory receptor on CD4+ T cells from human immunodeficiency virus-1-infected patients: Association with disease progression markers

The ability of the CD300a inhibitory receptor to modulate immune cell functions and its involvement in the pathogenesis of many diseases has aroused a great interest in this molecule. Within human CD4+ T lymphocytes from healthy donors, the inhibitory receptor CD300a is differentially expressed among different T helper subsets. However, there are no data about the expression and regulation of CD300a receptor on CD4+ T cells from human immunodeficiency virus (HIV)-infected patients. The objective of this study was to investigate the expression of CD300a on CD4+ T cells from HIV-infected patients on suppressive combined antiretroviral therapy (cART) and cART naïve patients. Our results have demonstrated that the expression levels of this inhibitory receptor were higher on CD4+ T cells from HIV infected subjects compared with healthy donors, and that cART did not reverse the altered expression of CD300a receptor in these patients. We have observed an increase of CD300a expression on both PD1+CD4+ and CD38+CD4+ T cells from HIV infected people. Interestingly, a triple positive (CD300a+PD1+CD38+) subset was expanded in naïve HIV infected patients, while it was very rare in healthy donors and patients on cART. Finally, we found a negative correlation of CD300a expression on CD4+ T lymphocytes and some markers associated with HIV disease progression. Thus, our results show that HIV infection has an impact in the regulation of CD300a inhibitory receptor expression levels, and further studies will shed light into the role of this cell surface receptor in the pathogenesis of HIV infection.This study was supported by a grant from “Plan Estatal de I + D + I 2013–2016, ISCIII-Subdirección de Evaluación y Fomento de la Investigación-Fondo Europeo de Desarrollo Regional (FEDER) (Grant PI13/00889)” and Marie Curie Actions, Career Integration Grant, European Commission (Grant CIG 631674). JV is recipient of a predoctoral contract funded by the Department of Education, Language Policy and Culture, Basque Government (PRE_2017_2_0242). JV and IT are recipients of a fellowship from the Jesús de Gangoiti Barrera Foundation (FJGB15/008 and FJGB17/003). LT-D was supported by Instituto de Salud Carlos III, PFIS (FI00/00431). OZ is recipient of a postdoctoral contract funded by “Instituto de Salud Carlos III-Contratos Sara Borrell 2017 (CD17/0128)” and the European Social Fund (ESF)-The ESF invests in your future. ER-M is supported by Programa Nicolás Monardes, C0032-2017, Consejería de Salud, Junta de Andalucía. FB is an Ikerbasque Research Professor, Ikerbasque, Basque Foundation for Science.Peer Reviewe

CD300a identifies a CD4(+)memory T cell subset with a higher susceptibility to HIV-1 infection

Human CD300a is known to promote the infection by dengue and other enveloped viruses and is overexpressed on CD4+ T cells from HIV-1-infected patients. We found that infected CD4+RA− T cells from untreated HIV-1-infected patients were mostly CD300a+. Furthermore, CD300a expressing CD4+RA− T cells from healthy donors were significantly more infected by HIV-1 in vitro than CD300a− cells. CD300a might represent a biomarker of susceptibility to HIV-1 infection on memory CD4+ T lymphocytes