The Role of Dendritic Cells in S. pneumoniae Transport to Follicular Dendritic Cells

Balthasar A. Heesters; Michael C. Carroll

doi:10.1016/j.celrep.2016.08.049

The Role of Dendritic Cells in S. pneumoniae Transport to Follicular Dendritic Cells

Balthasar A. Heesters^*
, Michael C. Carroll

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Affinity-mature B cells require cognate antigen, retained by follicular dendritic cells (FDCs), for clonal selection within germinal centers. Studies on how FDCs in lymphoid tissues acquire antigen have relied primarily on model protein antigens. To examine delivery of intact bacteria to FDCs, we used inactivated Streptococcus pneumonia (SP). We found that both medullary macrophages and a subset of SIGN-R1-positive dendritic cells (DCs) in the lymph node capture SP from the draining afferent lymphatics. The presence of DCs is required for initial complement activation, opsonization of the bacteria, and efficient transport of SP to FDCs. Moreover, we observed a major role for transport of bacteria to FDCs by naive B cells via a CD21-dependent pathway. We propose a mechanism by which efficient transport of SP to FDCs is dependent on DCs for initial binding and activation of complement and either direct transport to FDCs or transfer to naive B cells.

Original language	English
Pages (from-to)	3130-3137
Number of pages	8
Journal	Cell Reports
Volume	16
Issue number	12
DOIs	https://doi.org/10.1016/j.celrep.2016.08.049
Publication status	Published - 20 Sept 2016
Externally published	Yes

Bibliographical note

Funding Information:
We thank M. Nussenzweig (Rockefeller University) and U. von Andrian (Harvard Medical School) for CD11c-eYFP mice, R. Steinman (Rockefeller University) for the anti-SIGN-R1 hybridoma, M. Lipsitch (Harvard School of Public Health) for SP strain D39, S.F. Gonzalez for general guidance and help with EM, E.M. Carroll for technical assistance, and C.M. Frijlink for proofreading of the manuscript. This work was supported by the NIH (AI039246-19).

Publisher Copyright:
© 2016 The Author(s)

Funding

We thank M. Nussenzweig (Rockefeller University) and U. von Andrian (Harvard Medical School) for CD11c-eYFP mice, R. Steinman (Rockefeller University) for the anti-SIGN-R1 hybridoma, M. Lipsitch (Harvard School of Public Health) for SP strain D39, S.F. Gonzalez for general guidance and help with EM, E.M. Carroll for technical assistance, and C.M. Frijlink for proofreading of the manuscript. This work was supported by the NIH (AI039246-19).

Keywords

antigen transport
B cells
complement
dendritic cells
follicular dendritic cells
SIGN-R1
Streptococcus pneumoniae

Access to Document

10.1016/j.celrep.2016.08.049

Cite this

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title = "The Role of Dendritic Cells in S. pneumoniae Transport to Follicular Dendritic Cells",

abstract = "Affinity-mature B cells require cognate antigen, retained by follicular dendritic cells (FDCs), for clonal selection within germinal centers. Studies on how FDCs in lymphoid tissues acquire antigen have relied primarily on model protein antigens. To examine delivery of intact bacteria to FDCs, we used inactivated Streptococcus pneumonia (SP). We found that both medullary macrophages and a subset of SIGN-R1-positive dendritic cells (DCs) in the lymph node capture SP from the draining afferent lymphatics. The presence of DCs is required for initial complement activation, opsonization of the bacteria, and efficient transport of SP to FDCs. Moreover, we observed a major role for transport of bacteria to FDCs by naive B cells via a CD21-dependent pathway. We propose a mechanism by which efficient transport of SP to FDCs is dependent on DCs for initial binding and activation of complement and either direct transport to FDCs or transfer to naive B cells.",

keywords = "antigen transport, B cells, complement, dendritic cells, follicular dendritic cells, SIGN-R1, Streptococcus pneumoniae",

author = "Heesters, \{Balthasar A.\} and Carroll, \{Michael C.\}",

note = "Funding Information: We thank M. Nussenzweig (Rockefeller University) and U. von Andrian (Harvard Medical School) for CD11c-eYFP mice, R. Steinman (Rockefeller University) for the anti-SIGN-R1 hybridoma, M. Lipsitch (Harvard School of Public Health) for SP strain D39, S.F. Gonzalez for general guidance and help with EM, E.M. Carroll for technical assistance, and C.M. Frijlink for proofreading of the manuscript. This work was supported by the NIH (AI039246-19). Publisher Copyright: {\textcopyright} 2016 The Author(s)",

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N2 - Affinity-mature B cells require cognate antigen, retained by follicular dendritic cells (FDCs), for clonal selection within germinal centers. Studies on how FDCs in lymphoid tissues acquire antigen have relied primarily on model protein antigens. To examine delivery of intact bacteria to FDCs, we used inactivated Streptococcus pneumonia (SP). We found that both medullary macrophages and a subset of SIGN-R1-positive dendritic cells (DCs) in the lymph node capture SP from the draining afferent lymphatics. The presence of DCs is required for initial complement activation, opsonization of the bacteria, and efficient transport of SP to FDCs. Moreover, we observed a major role for transport of bacteria to FDCs by naive B cells via a CD21-dependent pathway. We propose a mechanism by which efficient transport of SP to FDCs is dependent on DCs for initial binding and activation of complement and either direct transport to FDCs or transfer to naive B cells.

AB - Affinity-mature B cells require cognate antigen, retained by follicular dendritic cells (FDCs), for clonal selection within germinal centers. Studies on how FDCs in lymphoid tissues acquire antigen have relied primarily on model protein antigens. To examine delivery of intact bacteria to FDCs, we used inactivated Streptococcus pneumonia (SP). We found that both medullary macrophages and a subset of SIGN-R1-positive dendritic cells (DCs) in the lymph node capture SP from the draining afferent lymphatics. The presence of DCs is required for initial complement activation, opsonization of the bacteria, and efficient transport of SP to FDCs. Moreover, we observed a major role for transport of bacteria to FDCs by naive B cells via a CD21-dependent pathway. We propose a mechanism by which efficient transport of SP to FDCs is dependent on DCs for initial binding and activation of complement and either direct transport to FDCs or transfer to naive B cells.

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KW - B cells

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KW - SIGN-R1

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