Myeloid cells limit production of antibody-secreting cells after immunization in the lymph node

David R. Fooksman, Michel C. Nussenzweig, Michael L. Dustin

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Ab-secreting cell (ASC) expansion and survival are important processes in optimizing vaccines and controlling autoimmunity. The microenvironment of the medullary cords is positioned to control these key processes. Previously, we imaged and characterized ASC differentiation and migration by intravital microscopy in the lymph node (LN) by transferring and activating B cells expressing yellow fluorescent protein only in the ASC compartment. In this study, we observed that yellow fluorescent protein+ ASCs in the medullary cords migrated along myelomonocytic cells and arrested in contact with them. Acute ablation of myeloid cells using the human diphtheria receptor system (diphtheria toxin receptor [DTR) expressed in Lysmd1-cre-positive cells increased ASC and Ab production by 2-fold. Increases in ASC numbers were associated with cell proliferation based on Ki-67 staining, rather than reduced apoptosis, or changes in egress from the LN. Using DTR-mediated ablation targeted to Ccr2-expressing myeloid cells also generated increases in ASCs. In contrast, neither the depletion of Gr-1-positive cells with an Ab nor the ablation of cells using a cd11c-DTR resulted in any change in ASCs. IL-6 cytokine signaling can enhance ASC production and has been implicated in dampening ASCs in lupus mouse models through myeloid cells. Using mixed bone marrow chimeras, we observed that IL-6 enhances ASC production, but IL-6 production was not required by myeloid cells to dampen ASCs in the LN. Inhibition of ASCs by these myeloid cells in the LN provides a new regulatory mechanism with implications for tuning Ab responses.

Original languageEnglish (US)
Pages (from-to)1004-1012
Number of pages9
JournalJournal of Immunology
Volume192
Issue number3
DOIs
StatePublished - Feb 1 2014

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Antibody-Producing Cells
Myeloid Cells
Immunization
Lymph Nodes
Interleukin-6
Diphtheria
Autoimmunity
Cell Movement
Cell Differentiation
Cell Survival
Proteins
B-Lymphocytes
Vaccines
Cell Count
Bone Marrow
Cell Proliferation
Apoptosis
Staining and Labeling
Cytokines

ASJC Scopus subject areas

  • Immunology

Cite this

Myeloid cells limit production of antibody-secreting cells after immunization in the lymph node. / Fooksman, David R.; Nussenzweig, Michel C.; Dustin, Michael L.

In: Journal of Immunology, Vol. 192, No. 3, 01.02.2014, p. 1004-1012.

Research output: Contribution to journalArticle

Fooksman, David R. ; Nussenzweig, Michel C. ; Dustin, Michael L. / Myeloid cells limit production of antibody-secreting cells after immunization in the lymph node. In: Journal of Immunology. 2014 ; Vol. 192, No. 3. pp. 1004-1012.
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