Balanced responsiveness to chemoattractants from adjacent zones determines B-cell position

Reif, Karin; Ekland, Eric H.; Ohl, Lars; Nakano, Hideki; Lipp, Martin; Förster, Reinhold; Cyster, Jason G.

doi:10.1038/416094a

Cited by 488 publications

(449 citation statements)

References 30 publications

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“…Of note, successful B cell responses to Tdependent antigens require that both cellular partners be in a state of "priming". This cellular co-localization correlates well with induction of CXCR5 expression on T cells and modulation of B cell responses to LN chemokines [12,13]. In humans, in vitro stimulation of naive CD4 + T cells results in the rapid and uniform induction of CXCR5 expression [14], suggesting that, similar to the situation in mice, priming of T cells in the T cell zone of human secondary lymphoid tissues also results in their relocation toward the B cell compartment.…”

Section: Introductionsupporting

confidence: 57%

B cells alter the phenotype and function of follicular‐homing CXCR5⁺ T cells

Ebert

Horn²,

Lang³

et al. 2004

Eur J Immunol

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The CXC chemokine receptor (CXCR)5 is rapidly induced on activated CD4 + T cells, allowing migration toward secondary lymphoid tissue follicles, where the CXCR5 ligand CXCL13/ BCA-1 is produced. Such CXCR5 + T cells provide efficient help for B cell immunoglobulin production and are termed follicular B helper T (T FH ) cells. However, the molecular mechanisms by which T FH cells provide B cell help are unknown. Here, we demonstrate that newly generated (antigen-primed) T FH cells express a phenotype consistent with induction of B cell proliferation, but co-culture with primed B cells resulted in a switch to a plasma cell-inducing phenotype, characterized by loss of CD154, induction of CD70 and an increase in IL-10 production capacity. The ability to produce IL-10 could be maintained as a stable phenotype, but its secretion was strictly dependent on inducible costimulator (ICOS) signaling. Furthermore, B cells preserved a lymph node migration phenotype in proliferating T FH cells by preventing the loss of CC chemokine receptor (CCR)7 and the induction of CCR5. Thus, B cells directly modulate the B cell helper phenotype in T FH cells and actively promote their prolonged co-localization with these cells.

show abstract

Section: Introductionsupporting

confidence: 57%

B cells alter the phenotype and function of follicular‐homing CXCR5⁺ T cells

Ebert

Horn²,

Lang³

et al. 2004

Eur J Immunol

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“…Activated B cells have been shown to move to the T cell zones in secondary lymphoid organs by up-regulating CCR7 expression, enabling chemotaxis towards CCL19 and CCL21 [20]. Along similar lines, DC also up-regulate CCR7 upon exposure to inflammatory stimuli, which enables trafficking to splenic and lymph node T cell zones [21,22].…”

Section: Discussionmentioning

confidence: 96%

Distinct in vivo dendritic cell activation by live versus killed Listeria monocytogenes

et al. 2005

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Immunization of mice with live or heat-killed Listeria monocytogenes (HKLM) efficiently primes pathogen-specific CD8 + T cells. T lymphocytes primed by HKLM, however, undergo attenuated proliferation and do not fully differentiate. Thus, only infection with live bacteria induces long-term, CD8 + T cell-mediated protective immunity. In this study we demonstrate that live and heat-killed bacteria, while both associating with Mac-3 + CD11b hi cells, localize to distinct splenic areas following intravenous inoculation. While HKLM localize to the marginal zone and the splenic red pulp, live L. monocytogenes are carried to the T cell zone of splenic white pulp. Despite these differences, in vivo depletion of CD11c-expressing cells prevents priming of naive T cells by either HKLM or live L. monocytogenes. Analysis of CD11c hi dendritic cells (DC) reveals that infection with live L. monocytogenes induces higher levels of CD40, CD80 and CD86 expression than immunization with HKLM. Our results suggest that CD8 + T cell priming following HKLM immunization or live infection is mediated by DC and that the disparate outcomes of priming can be attributed to suboptimal conditioning of DC in the absence of live, cytosol-invasive bacteria.

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“…Follicular B cells had increased CXCR5 expression but decreased migration towards CXCL13. Implying that aged B cells may have impaired downstream functioning from CXCR5, as one would anticipate increased CXCR5 expression to enhance migration towards CXCL13 33. Aged MZ B cells displayed increased migration to S1P, but the expression levels of S1P 1 and S1P in the sera were similar in young and old mice.…”

Section: Discussionmentioning

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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Balanced responsiveness to chemoattractants from adjacent zones determines B-cell position

Cited by 488 publications

References 30 publications

B cells alter the phenotype and function of follicular‐homing CXCR5⁺ T cells

B cells alter the phenotype and function of follicular‐homing CXCR5⁺ T cells

Distinct in vivo dendritic cell activation by live versus killed Listeria monocytogenes

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

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Balanced responsiveness to chemoattractants from adjacent zones determines B-cell position

Cited by 488 publications

References 30 publications

B cells alter the phenotype and function of follicular‐homing CXCR5+ T cells

B cells alter the phenotype and function of follicular‐homing CXCR5+ T cells

Distinct in vivo dendritic cell activation by live versus killed Listeria monocytogenes

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

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B cells alter the phenotype and function of follicular‐homing CXCR5⁺ T cells

B cells alter the phenotype and function of follicular‐homing CXCR5⁺ T cells