Follicular shuttling of marginal zone B cells facilitates antigen transport

Cinamon, Guy; Zachariah, Marcus; Lam, Olivia M; Foss, Frank W.; Cyster, Jason G.

doi:10.1038/ni1542

Cited by 444 publications

(514 citation statements)

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“…Binding of anti‐CD21‐PE mAb by some follicular B cells was also evident at this time (Fig. 3b), consistent with the presence of recirculating follicular B cells in the MZ and blood 3, 23. By 20 min after anti‐CD21‐PE mAb injection the frequency of PE + MZ B cells had increased to c. 80% in young mice (Fig.…”

Section: Resultssupporting

confidence: 76%

“…MZ B cells constantly shuttle between the follicle and MZ to collect blood‐borne complement‐opsonized antigens and deliver them to FDC in the B‐cell follicles 3, 21. At any time, typically 50% of the MZ B cells are in the MZ, the rest in the follicles 3.…”

Section: Resultsmentioning

confidence: 99%

“…At any time, typically 50% of the MZ B cells are in the MZ, the rest in the follicles 3. Whether the ageing‐related changes to the splenic MZ affected the follicular shuttling of MZ B cells was not known.…”

Section: Resultsmentioning

confidence: 99%

“…Whether the ageing‐related changes to the splenic MZ affected the follicular shuttling of MZ B cells was not known. To address this issue, an established antibody pulse‐labelling protocol was adopted to chronologically compare the frequency of these cells within the vascular compartment (MZ) and B‐cell follicles 3, 22. With this method a brief (5 min) intravenous exposure to PE‐conjugated anti‐CD21 monoclonal antibody (mAb) selectively labels the B cells exposed to peripheral blood (those within the MZ and bloodstream) by binding to their CD21.…”

Section: Resultsmentioning

confidence: 99%

“…By 20 min post‐injection with anti‐CD21‐PE mAb a greater proportion of the MZ B cells are labelled due to their migration between the follicles and MZ during the intervening period. Hence, by comparing the levels of PE + cells at intervals after intravenous anti‐CD21‐PE mAb treatment, the kinetics of B‐cell localization and shuttling between the MZ and follicles can be determined 3, 22…”

Section: Resultsmentioning

confidence: 99%

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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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Section: Resultssupporting

confidence: 76%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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

Turner

Mabbott

2017

Immunology

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Antibody Synthesis In Vitro

Iborra

Martı́nez

Palacio

2015

Encyclopedia of Life Sciences

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Antibodies are specific proteins that recognise nearly any chemical structure. During in vivo immunisation B cells are activated by antigen. Antigen‐specific cells proliferate and some differentiate into antibody‐secreting plasma cells. Monoclonal antibody technology was first reported by Köhler and Milstein in 1975. Briefly, B cells with specificity for a known antigen were fused with myeloma to make them immortal. Hybridomas grow in culture indefinitely and secrete monoclonal antibodies (mAbs) of a desired specificity. Hybridoma technology and antibody engineering have contributed in Biomedicine to the diagnosis of malignancies, tissue typing, identification of individual cell types, detection of cytokines, growth factors and hormones. The mAbs have become important in human immunotherapy and diagnosis. Murine mAbs have limited potential in human therapeutic applications due to human immune response to the murine antibodies. Several strategies for human mAbs production for immunotherapy are described in this article. Monoclonal antibodies have also a wide range of applications in Health and Food Sciences, Environmental Sciences, Technology and Experimental Sciences among others. Key Concepts Antigen is a molecule that binds specifically to B cell receptor (BCR) or soluble antibodies. T cell receptor (TCR) recognise processed antigen presented by MHC (major histocompatibility complex). Epitope or antigenic determinant is part of an antigen that is recognised specifically by TCR‐MHC or by BCR or by soluble antibodies. Immunogen is an antigen that generates a cellular and humoral immune response. Antibody is an immunoglobulin that recognises specifically a particular antigenic epitope. Antibody affinity is the strength of binding between a single binding site of an antibody and a single antigenic determinant or epitope. Plasma B cells are differentiated B cells that, after binding to an antigen, secrete soluble antibodies. Hybridoma is a hybrid cell line obtained by cell fusion of an immortalised lymphocyte tumor line, or myeloma, and B lymphocytes with defined antigen specificities. Monoclonal antibody is an immunoglobulin with specificity for one antigenic determinant or epitope, derived from a single B‐clone. Antibody immunotherapy is applied in immunopathology and in cancer. The main therapeutic agents are human or humanised monoclonal antibodies.

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Local Immunomodulatory Strategies to Prevent Allo‐Rejection in Transplantation of Insulin‐Producing Cells

et al. 2021

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Islet transplantation has shown promise as a curative therapy for type 1 diabetes (T1D). However, the side effects of systemic immunosuppression and limited long-term viability of engrafted islets, together with the scarcity of donor organs, highlight an urgent need for the development of new, improved, and safer cell-replacement strategies. Induction of local immunotolerance to prevent allo-rejection against islets and stem cell derived cells has the potential to improve graft function and broaden the applicability of cellular therapy while minimizing adverse effects of systemic immunosuppression. In this mini review, recent developments in non-encapsulation, local immunomodulatory approaches for T1D cell replacement therapies, including islet/ cell modification, immunomodulatory biomaterial platforms, and co-transplantation of immunomodulatory cells are discussed. Key advantages and remaining challenges in translating such technologies to clinical settings are identified. Although many of the studies discussed are preliminary, the growing interest in the field has led to the exploration of new combinatorial strategies involving cellular engineering, immunotherapy, and novel biomaterials. Such interdisciplinary research will undoubtedly accelerate the development of therapies that can benefit the whole T1D population.

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Follicular shuttling of marginal zone B cells facilitates antigen transport

Cited by 444 publications

References 44 publications

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

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

Antibody Synthesis In Vitro

Local Immunomodulatory Strategies to Prevent Allo‐Rejection in Transplantation of Insulin‐Producing Cells

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