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PMID: 12874264 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Macrophages control the retention and trafficking of B lymphocytes in the splenic marginal zone.

The Journal of experimental medicine ·Vol. 198 ·No. 2 ·2003-07-21 ·Pages 333-40

Karlsson MC, Guinamard R, Bolland S, Sankala M, Steinman RM, Ravetch JV

Abstract

The marginal zone of the spleen is a precisely ordered region that contains specialized subsets of B lymphocytes and macrophages. Disruption of the negative signaling inositol phosphatase, SH2-containing inositol-5-phosphatase 1 (SHIP), results in the loss of marginal zone B cells (MZBs) with reorganization of marginal zone macrophages (MZMOs) to the red pulp of the spleen. This primary macrophage defect, as revealed by selectively depleting SHIP in myeloid cells shows that MZMOs are specifically required for the retention of MZBs. The MZMO phenotype was reverted in SHIP/Bruton's tyrosine kinase (Btk) double knockout mice, thus identifying the Btk activating pathway as an essential component being regulated by SHIP. Furthermore, we identified a direct interaction between the MARCO scavenger receptor on MZMOs and MZBs. Activation or disruption of this interaction results in MZB migration to the follicle. The migration of the MZMOs was further studied after the response to Staphylococcus aureus, which induced MZMOs to move into the red pulp while MZBs migrated into the follicular zone. The marginal zone is therefore a dynamic structure in which retention and trafficking of B cells requires specific macrophage-B cell interactions.

MeSH Terms
Animals B-Lymphocyte Subsets/immunology B-Lymphocytes/cytology,immunology Flow Cytometry Macrophages/cytology,immunology Mice Mice, Inbred C57BL Mice, Knockout Models, Animal Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases Phosphoric Monoester Hydrolases/deficiency,genetics,immunology Spleen/cytology,immunology
Chemicals
Phosphoric Monoester Hydrolases INPPL1 protein, human Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Karlsson Mikael C I
Laboratory of Molecular Genetics and Immunology, The Rockefeller University, Box 98, 1230 York Avenue, New York, NY 10021, USA.
Guinamard Rodolphe
Bolland Silvia
Sankala Marko
Steinman Ralph M
Ravetch Jeffrey V
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
Published
2003-07-21
Pages
333-40
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2194070
Subset
IM
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