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Our Lab’s Research Focus

Our lab investigates how the immune system establishes long-lasting protection after infection, with a focus on B cell memory. During an immune response, B cells undergo activation and selection processes that lead to the generation of two key memory populations:

  • Long-lived plasma cells (LLPCs): These cells migrate to the bone marrow, where they continuously secrete high-affinity antibodies, providing durable protection that can last for years or even a lifetime.
  • Memory B cells (MBCs): These cells remain in a quiescent state in secondary lymphoid organs, such as the spleen and lymph nodes, until they encounter the same pathogen—or a variant—again. Upon reactivation, MBCs can rapidly differentiate into antibody-secreting plasma cells or re-enter germinal centers to further diversify the immune repertoire.

Traditionally, B cell memory has been studied in secondary lymphoid organs. However, recent work from our group and others has shown that LLPCs and MBCs can also take up residence in barrier tissues, such as the lungs, following mucosal infections like influenza and SARS-CoV-2. These populations appear to originate directly from germinal center reactions occurring in tertiary lymphoid structures within the tissue itself. Interestingly, the mechanisms governing germinal center selection and memory formation in barrier tissues seem to differ from those in classical lymphoid organs.

Understanding how B cell memory is generated and maintained in these tissues is essential for several reasons:

  1. Vaccine development: Many next-generation vaccines, including intranasal and oral formulations, aim to induce mucosal immunity. Defining how B cell responses are triggered directly in barrier sites will help optimize these strategies.
  2. Immune regulation in disease: While tissue-resident B cell populations can be protective during infection, they may also contribute to chronic inflammation or pathology, such as in allergic asthma.

Our research aims to uncover the signals and cellular interactions that drive germinal center reactions and memory B cell differentiation in barrier tissues like the lung and gut. By doing so, we hope to advance the development of vaccines and therapies that harness mucosal immunity while avoiding harmful immune responses.

Publications

2026
Holgado MP, Origlio S, Bertoia L, Moussa M, Trivedi A, Fiore F, Zarubica A, Slack E, Linterman MA, C..., Mucosal tissue cues shape B cell memory through the IgA BCR., Sci Immunol 2026 Jul; 11(121): eadv1149.
2026
Gaya M, Good-Jacobson KL, Molecular and tissue regulation of memory B cells., Sci Immunol 2026 Jul; 11(121): eaef3415.
2025
Laura Almada, Yamila N Gazzoni, Cristian G Beccaria, Facundo Fiocca Vernengo, Santiago Boccardo, Mel..., CD39 is an antibody-secreting B-cell marker that modulates germinal center and antibody responses during infection, Frontiers in Immunology.
2025
Clemence Ngo, Camille Pierini-Malosse, Khalissa Rahmani, Michael Valente, Nils Collinet, Gilles Bess..., Plasmacytoid dendritic cells are dispensable or detrimental in murine systemic or respiratory viral infections, Nat Immunol 2025 Sep; (): .
2025
Chenfei He, Shan Wang, Marion Moreews, Shengduo Pei, Guangchun Chen, Quan-Zhen Li, Alberto del Monte..., The balance between conventional and unconventional T follicular helper cells influences autoreactive B cell responses, Cell Reports.
2024
Clemence Ngo, Khalissa Rahmani, Michael Valente, Nils Collinet, Gilles Bessou, Manon Fabregue, Sarah..., Plasmacytoid dendritic cells are dispensable or detrimental in murine systemic or respiratory viral infections, 2024.
2023
Anais Joachim, Rudy Aussel, Léna Gélard, Fanghui Zhang, Daiki Mori, Claude Grégoire, Sergio Villa..., Defective LAT signalosome pathology in mice mimics human IgG4-related disease at single-cell level, <i>Journal of Experimental Medicine</i>, 2023, 220 (11), <a target="_blank" href="https://dx.doi.org/10.1084/jem.20231028">⟨10.1084/jem.20231028⟩</a>.
2022
Alan Courey-Ghaouzi, Mauro Gaya, Identification of Non-classical Follicular T Cells, .
2022
Marco Ataide, Konrad Knöpper, Paulina Cruz de Casas, Milas Ugur, Sarah Eickhoff, Mangge Zou, Haroon..., Lymphatic migration of unconventional T cells promotes site-specific immunity in distinct lymph nodes, Immunity.
2022
Claude Gregoire, Lionel Spinelli, Sergio Villazala-Merino, Laurine Gil, María Pía Holgado, Myriam ..., Viral infection engenders bona fide and bystander subsets of lung-resident memory B cells through a permissive mechanism, Immunity 2022 Jul; 55(7): 1216-1233.e9.
2022
Nicolas P, Ollier J, Mori D, Voisinne G, Celis-Gutierrez J, Gregoire C, Perroteau J, Vivien R, Camus..., Systems-level conservation of the proximal TCR signaling network of mice and humans., J Exp Med 2022 Feb; 219(2): .
2021
Mori D, Grégoire C, Voisinne G, Celis-Gutierrez J, Aussel R, Girard L, Camus M, Marcellin M, Argent..., The T cell CD6 receptor operates a multitask signalosome with opposite functions in T cell activation., J Exp Med 2021 Feb; 218(2): .
2020
Locard-Paulet M, Voisinne G, Froment C, Goncalves Menoita M, Ounoughene Y, Girard L, Gregoire C, Mor..., LymphoAtlas: a dynamic and integrated phosphoproteomic resource of TCR signaling in primary T cells reveals ITSN2 as a regulator of effector functions., Mol Syst Biol 2020 Jul; 16(7): e9524.
2019
Celis-Gutierrez J, Blattmann P, Zhai Y, Jarmuzynski N, Ruminski K, Grégoire C, Ounoughene Y, Fiore ..., Quantitative Interactomics in Primary T Cells Provides a Rationale for Concomitant PD-1 and BTLA Coinhibitor Blockade in Cancer Immunotherapy., Cell Rep 2019 Jun; 27(11): 3315-3330.e7.
2018
Tsui C, Martinez-Martin N, Gaya M, Maldonado P, Llorian M, Legrave NM, Rossi M, MacRae JI, Cameron A..., Protein Kinase C-β Dictates B Cell Fate by Regulating Mitochondrial Remodeling, Metabolic Reprogramming, and Heme Biosynthesis., Immunity 2018 Jun; 48(6): 1144-1159.e5.
2018
Sáez de Guinoa J, Jimeno R, Gaya M, Kipling D, Garzón MJ, Dunn-Walters D, Ubeda C, Barral P, CD1d-mediated lipid presentation by CD11c+ cells regulates intestinal homeostasis., EMBO J 2018 Mar; 37(5): .
2018
Gaya M, Barral P, Burbage M, Aggarwal S, Montaner B, Warren Navia A, Aid M, Tsui C, Maldonado P, Nai..., Initiation of Antiviral B Cell Immunity Relies on Innate Signals from Spatially Positioned NKT Cells., Cell 2018 Jan; 172(3): 517-533.e20.
2018
Burbage M, Gasparrini F, Aggarwal S, Gaya M, Arnold J, Nair U, Way M, Bruckbauer A, Batista FD, Tuning of in vivo cognate B-T cell interactions by Intersectin 2 is required for effective anti-viral B cell immunity., Elife 2018 Jan; 7(): .
2017
Martinez-Martin N, Maldonado P, Gasparrini F, Frederico B, Aggarwal S, Gaya M, Tsui C, Burbage M, Ke..., A switch from canonical to noncanonical autophagy shapes B cell responses., Science 2017 Feb; 355(6325): 641-647.
2016
Roncagalli R, Cucchetti M, Jarmuzynski N, Grégoire C, Bergot E, Audebert S, Baudelet E, Menoita MG,..., The scaffolding function of the RLTPR protein explains its essential role for CD28 co-stimulation in mouse and human T cells., J Exp Med 2016 Oct; 213(11): 2437-2457.
2016
Romain Roncagalli, Margot Cucchetti, Nicolas Jarmuzynski, Claude Grégoire, Elise Bergot, Stéphane ..., The scaffolding function of the RLTPR protein explains its essential role for CD28 co-stimulation in mouse and human T cells, <i>Journal of Experimental Medicine</i>, 2016, 213 (11), pp.2437-2457. <a target="_blank" href="https://dx.doi.org/10.1084/jem.20160579">⟨10.1084/jem.20160579⟩</a>.
2016
Laurence Ardouin, Hervé Luche, Rabie Chelbi, Sabrina Carpentier, Alaa Shawket, Frédéric Montañan..., Broad and Largely Concordant Molecular Changes Characterize Tolerogenic and Immunogenic Dendritic Cell Maturation in Thymus and Periphery, Immunity 2016 Aug; 45(2): 305-18.
2015
Gaya M, Castello A, Montaner B, Rogers N, Reis e Sousa C, Bruckbauer A, Batista FD, Host response. Inflammation-induced disruption of SCS macrophages impairs B cell responses to secondary infection., Science 2015 Feb; 347(6222): 667-72.
2015
Paster W, Bruger AM, Katsch K, Grégoire C, Roncagalli R, Fu G, Gascoigne NR, Nika K, Cohnen A, Fell..., A THEMIS:SHP1 complex promotes T-cell survival., EMBO J 2015 Feb; 34(3): 393-409.
2015
Navarro JM, Touzart A, Pradel LC, Loosveld M, Koubi M, Fenouil R, Le Noir S, Maqbool MA, Morgado E, ..., Site- and allele-specific polycomb dysregulation in T-cell leukaemia., Nat Commun 2015 Jan; 6(): 6094.
2015
Burbage M, Keppler SJ, Gasparrini F, Martínez-Martín N, Gaya M, Feest C, Domart MC, Brakebusch C, ..., Cdc42 is a key regulator of B cell differentiation and is required for antiviral humoral immunity., J Exp Med 2015 Jan; 212(1): 53-72.
2013
Castello A, Gaya M, Tucholski J, Oellerich T, Lu KH, Tafuri A, Pawson T, Wienands J, Engelke M, Bati..., Nck-mediated recruitment of BCAP to the BCR regulates the PI(3)K-Akt pathway in B cells., Nat Immunol 2013 Sep; 14(9): 966-75.
2013
Gaya M, Repetto V, Toneatto J, Anesini C, Piwien-Pilipuk G, Moreno S, Antiadipogenic effect of carnosic acid, a natural compound present in Rosmarinus officinalis, is exerted through the C/EBPs and PPARγ pathways at the onset of the differentiation program., Biochim Biophys Acta 2013 Jun; 1830(6): 3796-806.
2012
Christelle Langlet, Samira Tamoutounour, Sandrine Henri, Hervé Luche, Laurence Ardouin, Claude Gré..., CD64 expression distinguishes monocyte-derived and conventional dendritic cells and reveals their distinct role during intramuscular immunization., <i>Journal of Immunology</i>, 2012, 188 (4), pp.1751-60. <a target="_blank" href="https://dx.doi.org/10.4049/jimmunol.1102744">⟨10.4049/jimmunol.1102744⟩</a>.
2011
Emilie Narni-Mancinelli, Julie Chaix, Aurore Fenis, Yann M Kerdiles, Nadia Yessaad, Ana Reynders, Cl..., Fate mapping analysis of lymphoid cells expressing the NKp46 cell surface receptor., <i>Proceedings of the National Academy of Sciences of the United States of America</i>, 2011, 108 (45), pp.18324-9. <a target="_blank" href="https://dx.doi.org/10.1073/pnas.1112064108">⟨10.1073/pnas.1112064108⟩</a>.
2010
Roncagalli R, Mingueneau M, Grégoire C, Malissen M, Malissen B, LAT signaling pathology: an “autoimmune” condition without T cell self-reactivity., Trends Immunol 2010 Jul; 31(7): 253-9.
2010
Roncagalli R, Mingueneau M, Grégoire C, Langlet C, Malissen B, Malissen M, Lymphoproliferative disorders involving T helper effector cells with defective LAT signalosomes., Semin Immunopathol 2010 Jun; 32(2): 117-25.
2009
Mingueneau M, Roncagalli R, Grégoire C, Kissenpfennig A, Miazek A, Archambaud C, Wang Y, Perrin P, ..., Loss of the LAT adaptor converts antigen-responsive T cells into pathogenic effectors that function independently of the T cell receptor., Immunity 2009 Aug; 31(2): 197-208.
2009
Julien Gommeaux, Claude Grégoire, Prudence Nguessan, Mireille Richelme, Marie Malissen, Sylvie Guer..., Thymus-specific serine protease regulates positive selection of a subset of CD4+ thymocytes., <i>European Journal of Immunology</i>, 2009, 39 (4), pp.956-64. <a target="_blank" href="https://dx.doi.org/10.1002/eji.200839175">⟨10.1002/eji.200839175⟩</a>.
2008
Mingueneau M, Sansoni A, Grégoire C, Roncagalli R, Aguado E, Weiss A, Malissen M, Malissen B, The proline-rich sequence of CD3epsilon controls T cell antigen receptor expression on and signaling potency in preselection CD4+CD8+ thymocytes., Nat Immunol 2008 May; 9(5): 522-32.
2007
Claude Grégoire, Sarka Simova, Ying Wang, Amandine Sansoni, Sylvie Richelme, Anja Schmidt-Giese, Lu..., Deletion of the LIME adaptor protein minimally affects T and B cell development and function., <i>European Journal of Immunology</i>, 2007, 37 (11), pp.3259-69. <a target="_blank" href="https://dx.doi.org/10.1002/eji.200737563">⟨10.1002/eji.200737563⟩</a>.
2005
Ying Wang, Ondrej Horvath, Andrea Hamm-Baarke, Mireille Richelme, Claude Grégoire, Rodolphe r. Gu..., Single and Combined Deletions of the NTAL/LAB and LAT Adaptors Minimally Affect B-Cell Development and Function, <i>Molecular and Cellular Biology</i>, 2005, 25 (11), pp.4455-4465. <a target="_blank" href="https://dx.doi.org/10.1128/mcb.25.11.4455-4465.2005">⟨10.1128/mcb.25.11.4455-4465.2005⟩</a>.
1991
D. Emilie, M. Matthes, C. Gregoire, F. Letourneur, Am Wegener, Jf Nicolas, Bernard Malissen, Fluorescence-based monitoring of interleukin-2 gene expression., <i>Immunological Reviews</i>, 1991, 119, pp.95-103.

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