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J Exp Med. 2017 Sep 4;214(9):2777-2794. doi: 10.1084/jem.20161122. Epub 2017 Jul 11.

Blimp-1-dependent and -independent natural antibody production by B-1 and B-1-derived plasma cells.

Author information

1
Graduate Group in Immunology, University of California, Davis, Davis, CA.
2
Center for Comparative Medicine, University of California, Davis, Davis, CA.
3
Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, Davis, CA.
4
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL.
5
Graduate Group in Immunology, University of California, Davis, Davis, CA nbaumgarth@ucdavis.edu.

Abstract

Natural antibodies contribute to tissue homeostasis and protect against infections. They are secreted constitutively without external antigenic stimulation. The differentiation state and regulatory pathways that enable continuous natural antibody production by B-1 cells, the main cellular source in mice, remain incompletely understood. Here we demonstrate that natural IgM-secreting B-1 cells in the spleen and bone marrow are heterogeneous, consisting of (a) terminally differentiated B-1-derived plasma cells expressing the transcriptional regulator of differentiation, Blimp-1, (b) Blimp-1+, and (c) Blimp-1neg phenotypic B-1 cells. Blimp-1neg IgM-secreting B-1 cells are not simply intermediates of cellular differentiation. Instead, they secrete similar amounts of IgM in wild-type and Blimp-1-deficient (PRDM-1ΔEx1A) mice. Blimp-1neg B-1 cells are also a major source of IgG3. Consequently, deletion of Blimp-1 changes neither serum IgG3 levels nor the amount of IgG3 secreted per cell. Thus, the pool of natural antibody-secreting B-1 cells is heterogeneous and contains a distinct subset of cells that do not use Blimp-1 for initiation or maximal antibody secretion.

PMID:
28698287
PMCID:
PMC5584113
DOI:
10.1084/jem.20161122
[Indexed for MEDLINE]
Free PMC Article

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