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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 publication

DOI

10.4049/jimmunol.1300977

Type

Journal article

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Date

02/2014

Volume

192

Pages

1004 - 1012

Addresses

Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016;

Keywords

Lymph Nodes, Antibody-Producing Cells, B-Lymphocyte Subsets, Myeloid Cells, Animals, Animals, Congenic, Mice, Inbred C57BL, Radiation Chimera, Mice, Transgenic, Humans, Mice, Diphtheria Toxin, Intercellular Signaling Peptides and Proteins, Ovalbumin, Luminescent Proteins, Ki-67 Antigen, Recombinant Fusion Proteins, Transcription Factors, Interleukin-6, Immunization, Adoptive Transfer, Cell Communication, Apoptosis, Genes, Reporter, Receptors, CCR2, Promoter Regions, Genetic, Heparin-binding EGF-like Growth Factor