CD137 is required for M cell functional maturation but not lineage commitment.
Mucosal immune surveillance depends on M cells that reside in the epithelium overlying Peyer's patch and nasopharyngeal associated lymphoid tissue to transport particles to underlying lymphocytes. M cell development is associated with B lymphocytes in a basolateral pocket, but the interactions between these cells are poorly understood. In a cell culture model of M cell differentiation, we found lymphotoxin/tumor necrosis factor alpha induction of CD137 (TNFRSF9) protein on intestinal epithelial cell lines, raising the possibility that CD137 on M cells in vivo might interact with CD137L expressed by B cells. Accordingly, while CD137-deficient mice produced UEA-1+ M cell progenitors in nasopharyngeal associated lymphoid tissue and Peyer's patch epithelium, they showed an abnormal morphology, including the absence of basolateral B cell pockets. More important, CD137-deficient nasopharyngeal associated lymphoid tissue M cells were defective in microparticle transcytosis. Bone marrow irradiation chimeras confirmed that while induction of UEA-1+ putative M cell precursors was not CD137-dependent, full M cell transcytosis function required expression of CD137 by radioresistant stromal cells as well as by bone marrow-derived cells. These results are consistent with a two-step model of M cell differentiation, with initial CD137-independent commitment to the M cell lineage followed by a CD137-CD137L interaction of M cells with CD137-activated B lymphocytes or dendritic cells for functional maturation.
Hsieh
En Hui
EH
Division of Biomedical Sciences, University of California, Riverside, Riverside, CA 92521, USA.
Fernandez
Xiomara
X
Wang
Jing
J
Hamer
Mary
M
Calvillo
Stephanie
S
Croft
Michael
M
Kwon
Byoung S
BS
Lo
David D
DD
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D018938:Caco-2 Cells; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D019070:Cell Lineage; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology; D008221:Lymphoid Tissue / Q000166:cytology* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009305:Nasopharynx / Q000033:anatomy & histology; D010581:Peyer's Patches / Q000166:cytology* / Q000276:immunology; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha