Germinal center dark and light zone organization is mediated by CXCR4 and CXCR5

Allen, Christopher D.C.; Ansel, K. Mark; Low, Caroline M. R.; Lesley, Robin; Tamamura, Hirokazu; Fujii, Nobutaka; Cyster, Jason G.

doi:10.1038/ni1100

Cited by 650 publications

(752 citation statements)

References 44 publications

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“…Th e expression of CCR7 on the iGB cells was as similar to na ï ve follicular B cells ( Supplementary Fig. S1 ), as reported for mouse GC B 36 , and unlike the high CCR7 levels seen on activated B cells 37 . Th us, we call these B cells propagated on 40LB cells in-vitro -induced GC B (iGB) cells.…”

Section: Resultssupporting

confidence: 78%

In-vitro derived germinal centre B cells differentially generate memory B or plasma cells in vivo

et al. 2011

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In response to T cell-dependent antigens, B cells proliferate extensively to form germinal centres (GC), and then differentiate into memory B (B mem ) cells or long-lived plasma cells (LLPCs) by largely unknown mechanisms. Here we show a new culture system in which mouse na ï ve B cells undergo massive expansion and isotype switching, and generate GC-phenotype B (iGB) cells. The iGB cells expressing IgG1 or IgM / D, but not IgE, differentiate into B mem cells in vivo after adoptive transfer and can elicit rapid immune responses with the help of cognate T cells. Secondary culture with IL-21 maintains the proliferation of the iGB cells, while shifting their in vivo developmental fate from B mem cells to LLPCs, an outcome that can be reversed by withdrawal of IL-21 in tertiary cultures. Thus, this system enables in vitro manipulation of B-cell fate, into either B mem cells or LLPCs, and will facilitate dissection of GC-B cell differentiation programs.

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Section: Resultssupporting

confidence: 78%

In-vitro derived germinal centre B cells differentially generate memory B or plasma cells in vivo

et al. 2011

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“…Protocol was adapted from previously published procedures2, 16 as follows. Splenocytes were made into a single‐cell suspension by passing through a 0·7‐μ m cell strainer (ThermoFisher Scientific) and red cell lysed.…”

Section: Methodsmentioning

confidence: 99%

Ageing adversely affects the migration and function of marginal zone B cells

Turner

Mabbott

2017

Immunology

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SummaryMarginal zone (MZ) B cells are positioned within the spleen to capture blood‐borne antigen and immune complexes and deliver them to follicular dendritic cells in the B‐cell follicles. We show that within the spleens of aged mice antigen capture by MZ B cells, and their ability to shuttle between the follicle and MZ, were impaired. The ability of aged MZ B cells to migrate towards the MZ chemoattractant sphingosine‐1‐phosphate was increased, suggesting that aged MZ B cells had a greater propensity to be retained within the MZ. An extrinsic impairment in aged B‐cell migration towards the MZ was demonstrated using bone marrow chimeras. The follicular shuttling of MZ B cells derived from either young or aged bone marrow was similarly reduced in aged recipient spleens, showing that ageing effects on splenic stromal cells were responsible for the impaired follicular shuttling of MZ B cells. MZ B cells rapidly mount T‐cell‐independent (TI) antibody‐responses to microbial polysaccharide antigen. In aged mice the ability to produce immunoglobulins in response to the TI type 1 antigen TNP‐LPS was impaired. These ageing‐related changes to the MZ and MZ B cells have implications for the clearance of blood‐borne pathogens. Indeed elderly people have increased susceptibility to Streptococcus pneumoniae, a TI antigen, and decreased responses to vaccination. A thorough analysis of the mechanisms that underpin the ageing‐related decline in the status of the MZ and MZ B cells will help the design of novel treatments to improve immunity in the elderly.

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“…Similarly, chemokines CCL19 and CXCL12 drive lymphocyte recruitment and the positioning of follicular DCs, B cells and plasma cells at germinal centres 48. Here, an elegant cooperation between CXCL12 and CXCL13 directs the movement of B cells from the dark zone into the light zone as they mature into antibody‐secreting plasma cells 51. Hence homeostatic and certain inflammatory chemokines contribute to both the initiation of ELF development, the cellular organization required for their function as germinal centres.…”

Section: Homeostatic Chemokines In Elf Developmentmentioning

confidence: 99%

Ectopic lymphoid follicles: inducible centres for generating antigen‐specific immune responses within tissues

2015

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SummaryLymphoid neogenesis is traditionally viewed as a pre‐programmed process that promotes the formation of lymphoid organs during development. Here, the spatial organization of T and B cells in lymph nodes and spleen into discrete structures regulates antigen‐specific responses and adaptive immunity following immune challenge. However, lymphoid neogenesis is also triggered by chronic or persistent inflammation. Here, ectopic (or tertiary) lymphoid organs frequently develop in inflamed tissues as a response to infection, auto‐immunity, transplantation, cancer or environmental irritants. Although these structures affect local immune responses, the contribution of these lymphoid aggregates to the underlining pathology are highly context dependent and can elicit either protective or deleterious outcomes. Here we review the cellular and molecular mechanisms responsible for ectopic lymphoid neogenesis and consider the relevance of these structures in human disease.

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Germinal center dark and light zone organization is mediated by CXCR4 and CXCR5

Cited by 650 publications

References 44 publications

In-vitro derived germinal centre B cells differentially generate memory B or plasma cells in vivo

In-vitro derived germinal centre B cells differentially generate memory B or plasma cells in vivo

Ageing adversely affects the migration and function of marginal zone B cells

Ectopic lymphoid follicles: inducible centres for generating antigen‐specific immune responses within tissues

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