Recycling of memory B cells between germinal center and lymph node subcapsular sinus supports affinity maturation to antigenic drift

Zhang, Yang; Garcia-Ibanez, Laura; Ulbricht, Carolin; Lok, Laurence S.C.; Pike, Jeremy; Mueller-Winkler, Jennifer; Dennison, Thomas W.; Ferdinand, John R.; Burnett, Cameron J M; Yam‐Puc, Juan Carlos; Zhang, Lingling; Takahama, Yousuke; Ohigashi, Izumi; Brown, Geoffrey; Kurosaki, Tomohiro; Tybulewicz, Victor L. J.; Rot, Antal; Hauser, Anja E.; Clatworthy, Menna R.; Toellner, Kai‐Michael

doi:10.1038/s41467-022-29978-y

Cited by 24 publications

(22 citation statements)

References 73 publications

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“…Lymph nodes were obtained from various groups, sectioned, and stained as described previously ( 76 , 77 ). Briefly, lymph nodes were placed in 10 ml of 4% paraformaldehyde (PFA) for a 1h duration and then transferred into 30%, 20%, and 10% sucrose solutions gradually for dehydration at 4°C.…”

Section: Methodsmentioning

confidence: 99%

LigA formulated in AS04 or Montanide ISA720VG induced superior immune response compared to alum, which correlated to protective efficacy in a hamster model of leptospirosis

et al. 2022

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Leptospirosis is a zoonotic disease of global importance. The current vaccine provides serovar-specific and short-term immunity and does not prevent bacterial shedding in infected animals. Subunit vaccines based on surface proteins have shown to induce protection in an animal model. However, these proteins were tested with non-clinical adjuvants and induced low to moderate protective efficacy. We formulated a variable region of Leptospira immunoglobulin-like protein A (LAV) in clinical adjuvants, AS04 and Montanide ISA720VG, and then evaluated the immune response in mice and protective efficacy in a hamster model. Our results show that animals immunized with LAV-AS04 and LAV-Montanide ISA720VG (LAV-M) induced significantly higher levels of LAV-specific antibodies than LAV-Alum. While LAV-Alum induced Th2 response with the induction of IgG1 and IL-4, AS04 and LAV-M induced a mixed Th1/Th2 response with significant levels of both IgG1/IL-4 and IgG2c/IFN-γ. Both LAV-AS04 and LAV-M induced the generation of a significantly higher number of cytotoxic T cells (CTLs). The immune response in LAV-AS04- and LAV-M-immunized animals was maintained for a long period (>180 days) with the generation of a significant level of B- and T-cell memory. The strong immune response by both vaccines correlated to enhanced recruitment and activation of innate immune cells particularly DCs at draining lymph nodes and the formation of germinal centers (GCs). Furthermore, the immune response generated in mice correlated to protective efficacy in the hamster model of leptospirosis. These results indicate that LAV-AS04 and LAV-M are promising vaccines and can be further evaluated in clinical trials.

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Section: Methodsmentioning

confidence: 99%

LigA formulated in AS04 or Montanide ISA720VG induced superior immune response compared to alum, which correlated to protective efficacy in a hamster model of leptospirosis

et al. 2022

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“…B cell behavior in mouse LNs has been visualized by intravital imaging and advanced microscopy techniques. The results show that many memory B cells exit via the SCS [57]. In the SCS, B memory cells may take up antigens from SCS macrophages and reenter germinal centers using CCL21 gradients mediated by ACKR4 [57].…”

Section: Trends In Immunologymentioning

confidence: 90%

“…The results show that many memory B cells exit via the SCS [57]. In the SCS, B memory cells may take up antigens from SCS macrophages and reenter germinal centers using CCL21 gradients mediated by ACKR4 [57]. Alternatively, memory B cells drain out from the LN via the subcapsular and medullary sinuses [57].…”

Section: Trends In Immunologymentioning

confidence: 96%

“…In the SCS, B memory cells may take up antigens from SCS macrophages and reenter germinal centers using CCL21 gradients mediated by ACKR4 [57]. Alternatively, memory B cells drain out from the LN via the subcapsular and medullary sinuses [57]. The cell-specific differences in migration pathways suggest that T and B lymphocytes express different sets of trafficguiding molecules.…”

Section: Trends In Immunologymentioning

confidence: 99%

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Lymph node lymphatic endothelial cells as multifaceted gatekeepers in the immune system

Salmi

Jalkanen

2023

Trends in Immunology

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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: 99%

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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Recycling of memory B cells between germinal center and lymph node subcapsular sinus supports affinity maturation to antigenic drift

Cited by 24 publications

References 73 publications

LigA formulated in AS04 or Montanide ISA720VG induced superior immune response compared to alum, which correlated to protective efficacy in a hamster model of leptospirosis

LigA formulated in AS04 or Montanide ISA720VG induced superior immune response compared to alum, which correlated to protective efficacy in a hamster model of leptospirosis

Lymph node lymphatic endothelial cells as multifaceted gatekeepers in the immune system

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

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