B Cells Are Crucial for Both Development and Maintenance of the Splenic Marginal Zone

The splenic marginal zone is a unique compartment that separates the lymphoid white pulp from the surrounding red pulp. Due to the orchestration of specialized macrophages and B cells flanking a marginal sinus, this compartment plays an important role in uptake of blood-borne Ags and it gives the sp...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2004-03, Vol.172 (6), p.3620-3627
Main Authors: Nolte, Martijn A, Arens, Ramon, Kraus, Manfred, van Oers, Marinus H. J, Kraal, Georg, van Lier, Rene A. W, Mebius, Reina E
Format: Article
Language:English
Subjects:
Animals
Antigens, CD - genetics
B-Lymphocytes - cytology
B-Lymphocytes - immunology
B-Lymphocytes - metabolism
B-Lymphocytes - pathology
CD27 Ligand
CD70 antigen
Cell Death - genetics
Cell Death - immunology
Cell Differentiation - genetics
Cell Differentiation - immunology
Cells, Cultured
Humans
Immunophenotyping
Lymphocyte Depletion
Lymphopenia - genetics
Lymphopenia - immunology
Lymphopenia - pathology
Lymphotoxin-alpha - biosynthesis
Macrophages - pathology
marginal zone
Membrane Proteins - deficiency
Membrane Proteins - genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Mutant Strains
Mice, Transgenic
Spleen - anatomy & histology
Spleen - cytology
Spleen - immunology
Spleen - metabolism
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Summary:The splenic marginal zone is a unique compartment that separates the lymphoid white pulp from the surrounding red pulp. Due to the orchestration of specialized macrophages and B cells flanking a marginal sinus, this compartment plays an important role in uptake of blood-borne Ags and it gives the spleen its specialized function in antibacterial immunity. In this study, we demonstrate that both development and maintenance of this marginal zone is highly dependent on the presence of B cells. Spleens from B cell-deficient mice were found to lack both metallophilic and marginal zone macrophages as well as mucosal addressin cellular adhesion molecule-1+ sinus lining cells. Using an inducible Cre/loxP-driven mouse model in which mature B cells could be partially depleted by removal of the B cell receptor subunit Igalpha, we could show that the integrity and function of an established marginal zone was also dependent on the presence of B cells. This was confirmed in a transgenic model in which all B cells were gradually depleted due to overexpression of the TNF family member CD70. The loss of all cellular subsets from the marginal zone in these CD70 transgenic mice was effectively prevented by crossing these mice on a CD27(-/-) or TCRalpha(-/-) background, because this prohibited the ongoing B cell depletion. Therefore, we conclude that B cells are not only important for the development, but also for maintenance, of the marginal zone. This direct correlation between circulating B cells and the function of the spleen implies an increased risk for B cell lymphopenic patients with bacterial infections.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.172.6.3620