Viral infection engenders bona fide and bystander subsets of lung-resident memory B cells through a permissive mechanism

Grégoire, Claude; Spinelli, Lionel; Villazala-Merino, Sergio; Gil, Laurine; Holgado, María Pía; Moussa, Myriam; Dong, Chuang; Zarubica, Ana; Fallet, Mathieu; Navarro, Jean-Marc; Malissen, Bernard; Milpied, Pierre; Gaya, Mauro

doi:10.1016/j.immuni.2022.06.002

Cited by 26 publications

(33 citation statements)

References 50 publications

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“…However, the observation that the percentage of CXCR3 + atypical B cells does not change over time with minimal parasite exposure suggests that the expression of this marker by itself does not direct homing of B cells to tissues. This notion is strengthened by the recent finding that CXCR3 ablation in murine B cells has no effect on the establishment and maintenance of lung-resident memory B cells (47). Instead, CXCR3 should probably be considered a marker of activation or prior activation.…”

Section: Discussionmentioning

confidence: 99%

Atypical B cells consist of subsets with distinct effector functions

Reyes

Batugedara

Dutta

et al. 2022

Preprint

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Atypical B cells are a population of activated B cells that are commonly enriched in individuals with chronic immune activation. Prior studies to determine the function of these cells have yielded conflicting results, possibly due to functional heterogeneity among this B cell population. To better define the role(s) of atypical B cells in the host adaptive immune response, we performed single-cell sequencing of transcriptomes, cell surface markers, and B cell receptors in individuals with chronic Plasmodium falciparum exposure, a condition known to lead to accumulation of circulating atypical B cells. Our studies identified previously uncharacterized populations of atypical B cells with distinct transcriptional and functional profiles: i) anergy or tolerance, ii) increased ability to interact with T cells, and iii) preparation for high translational activity as seen in pre-antibody secreting cells. We identified a set of cell surface markers to distinguish these distinct atypical B cell subsets and confirmed their presence in malaria-experienced children and adults using flow cytometry. P. falciparum-specific cells were present in equal proportions within each of these populations, indicating that all three subsets develop in response to antigen stimulation. Collectively, our findings help explain the conflicting observations in prior studies involving the functions of atypical B cells and indicate the need for reclassification of these cells into multiple distinct subsets to better understand their role in the adaptive immune response in chronic inflammatory conditions.

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Section: Discussionmentioning

confidence: 99%

Atypical B cells consist of subsets with distinct effector functions

Reyes

Batugedara

Dutta

et al. 2022

Preprint

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“…Three main signatures of memory B cells were identified. These signatures share memory-associated markers such as Cd38, Ly6d, Klf2, Mndal and Sell, and cell migration genes such as Gp138, S1pr1, Ccr6 and Ccr7 which are all reported to be overexpressed on memory B cells with respect to GC B cells (33)(34)(35). Cluster 0 represents the largest resting memory B cell pool followed by innate-like memory cells expressing genes such as Fcrl5, Ptpn22 and Plac8 (cluster 3), and cluster 4 with an IFN-signature, marked by overexpression of Stat1, Irgm1 and Irf1.…”

Section: Three Different Signatures Of Memory B Cells Were Identified...mentioning

confidence: 98%

The whole-cell pertussis vaccine imposes a broad effector B cell response in mouse heterologous prime-boost settings

Valeri¹,

Sochon²,

Cousu³

et al. 2022

JCI Insight

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Since the introduction of new generation pertussis vaccines, resurgence of pertussis is observed in many developed countries. Former whole-cell pertussis vaccines (wP) are able to protect against disease and transmission but have been replaced in several industrialized countries 2 because of their reactogenicity and adverse effects. Current acellular pertussis vaccines (aP), made of purified proteins of Bordetella pertussis, are efficient at preventing disease but fail to induce long-term protection from infection. While the systemic and mucosal T cell immunity induced by the two types of vaccines has been well described, much less is known concerning B cell responses. Taking advantage of an inducible AID fate-mapping mouse model, we compared effector and memory B cells induced by the two classes of vaccines and showed that a stronger and broader memory B cell and plasma cell response is achieved by a wP prime. We also observed that homologous or heterologous vaccine combinations that include at least one wP administration, even as a booster dose, are sufficient to induce this broad effector response, thus highlighting its dominant imprint on the B cell profile. Finally, we describe the settlement of memory B cell populations in the lung following subcutaneous wP prime vaccination.

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“…and Gregoire et al. did not identify any defective recruitment of CXCR3 −/− B cells to the lungs [48, 65], however Oh et al. used a B‐cell specific KO of CXCR3 and could detect defective recruitment of IgA + B cells and overall decreased BRM number [68].…”

Section: Mbc In Mucosal Tissuesmentioning

confidence: 99%

“…In general, lung BRM exhibit a decrease in lymphoid recruitment markers, like Sell, and tissue egress markers, like S1pr1 [28,65]. On the other hand, lung BRM increase the expression of chemokine markers like Cxcr3, Ccr6, Ccr1 (all chemokine receptors), and Cd69 [28,48,64,65]. CD69 has also been suggested as a tissue residency marker for human MBC, given its wellestablished function for T cells tissue residency [64][65][66][67].…”

Section: Distinctive Features Of Brmmentioning

confidence: 99%

“…This could be deducted simply by the timing of iBALT formation, which takes approximately 14 days after infection [65,70,71]; by then, MBC are already being produced from lymphoid organs and ready to disseminate [7,28,60]. Several studies have further confirmed this hypothesis by analyzing the B cells repertoire of BRM, other MBC, and GC B cells in lymphoid organs or iBALT [28,48,65]. Indeed, the main contributors for lung BRM are mediastinal lymph nodes and spleen [28].…”

Section: Brm Origin and Tissue Localizationmentioning

confidence: 99%

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Memory B‐cell diversity: From early generation to tissue residency and reactivation

Reusch

Angeletti

2023

Eur J Immunol

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Memory B cells (MBCs) have a crucial function in providing an enhanced response to repeated infections. Upon antigen encounter, MBC can either rapidly differentiate to antibody secreting cells or enter germinal centers (GC) to further diversify and affinity mature. Understanding how and when MBC are formed, where they reside and how they select their fate upon reactivation has profound implications for designing strategies to improve targeted, next‐generation vaccines. Recent studies have crystallized much of our knowledge on MBC but also reported several surprising discoveries and gaps in our current understanding. Here, we review the latest advancements in the field and highlight current unknowns. In particular, we focus on timing and cues leading to MBC generation before and during the GC reaction, discuss how MBC become resident in mucosal tissues, and finally, provide an overview of factors shaping MBC fate‐decision upon reactivation in mucosal and lymphoid tissues.

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Viral infection engenders bona fide and bystander subsets of lung-resident memory B cells through a permissive mechanism

Cited by 26 publications

References 50 publications

Atypical B cells consist of subsets with distinct effector functions

Atypical B cells consist of subsets with distinct effector functions

The whole-cell pertussis vaccine imposes a broad effector B cell response in mouse heterologous prime-boost settings

Memory B‐cell diversity: From early generation to tissue residency and reactivation

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