Expression of Delta-like 1 in the splenic non-hematopoietic cells is essential for marginal zone B cell development

Yin, Shenghua; Yahata, Takashi; Negishi, Naoko; Nakano, Yasuhiro; Habu, Sonoko; Hozumi, Katsuto; Ando, Kiyoshi

doi:10.1016/j.imlet.2008.08.001

Cited by 23 publications

(27 citation statements)

References 20 publications

(29 reference statements)

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“…The T2 transitional B cell is thought to be the common precursor for both MZ B and follicular B-2 B cells [4]. Studies on gene-targeted mice have allowed the identification of several MZB cell determinants [5], [6], [7], [8], [9], [10], including effectors of Notch [11], [12], [13], [14], [15], [16], [17] and BCR [18], [19], although their contribution to MZB cell establishment/maintenance remains poorly understood [3], [20].…”

Section: Introductionmentioning

confidence: 99%

The Endocytic Adaptor Eps15 Controls Marginal Zone B Cell Numbers

Pozzi

Amodio²,

Lucano³

et al. 2012

PLoS ONE

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Eps15 is an endocytic adaptor protein involved in clathrin and non-clathrin mediated endocytosis. In Caenorhabditis elegans and Drosophila melanogaster lack of Eps15 leads to defects in synaptic vesicle recycling and synapse formation. We generated Eps15-KO mice to investigate its function in mammals. Eps15-KO mice are born at the expected Mendelian ratio and are fertile. Using a large-scale phenotype screen covering more than 300 parameters correlated to human disease, we found that Eps15-KO mice did not show any sign of disease or neural deficits. Instead, altered blood parameters pointed to an immunological defect. By competitive bone marrow transplantation we demonstrated that Eps15-KO hematopoietic precursor cells were more efficient than the WT counterparts in repopulating B220+ bone marrow cells, CD19− thymocytes and splenic marginal zone (MZ) B cells. Eps15-KO mice showed a 2-fold increase in MZ B cell numbers when compared with controls. Using reverse bone marrow transplantation, we found that Eps15 regulates MZ B cell numbers in a cell autonomous manner. FACS analysis showed that although MZ B cells were increased in Eps15-KO mice, transitional and pre-MZ B cell numbers were unaffected. The increase in MZ B cell numbers in Eps15 KO mice was not dependent on altered BCR signaling or Notch activity. In conclusion, in mammals, the endocytic adaptor protein Eps15 is a regulator of B-cell lymphopoiesis.

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Section: Introductionmentioning

confidence: 99%

The Endocytic Adaptor Eps15 Controls Marginal Zone B Cell Numbers

Pozzi

Amodio²,

Lucano³

et al. 2012

PLoS ONE

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“…Little is known regarding how Notch2 expression is regulated in MZ B cells, but its function is dependent upon binding to its ligand Delta-like 1 (20, 58). Delta-like 1 expression by splenic non-hematopoietic cells, likely a stromal cell, is sufficient to drive MZ B cell differentiation (63). The site of MZ commitment is unknown, but it likely occurs outside of the MZ.…”

Section: Discussionmentioning

confidence: 99%

Gut Microbial Dysbiosis Due to Helicobacter Drives an Increase in Marginal Zone B Cells in the Absence of IL-10 Signaling in Macrophages

Ray

Basu

Gharaibeh

et al. 2015

The Journal of Immunology

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It is clear that IL-10 plays an essential role in maintaining homeostasis in the gut in response to the microbiome. However, it is unknown whether IL-10 also facilitates immune homeostasis at distal sites. To address this question, we asked whether splenic immune populations were altered in IL-10-deficient (Il10−/−) mice in which differences in animal husbandry history were associated with susceptibility to spontaneous enterocolitis that is microbiome-dependent. The susceptible mice exhibited a significant increase in splenic macrophages, neutrophils and marginal zone (MZ) B cells that was inhibited by IL-10 signaling in myeloid, but not B cells. The increase in macrophages was due to increased proliferation that correlated with a subsequent enhancement in MZ B cell differentiation. Cohousing and antibiotic treatment studies suggested that the alteration in immune homeostasis in the spleen was microbiome-dependent. 16S rRNA sequencing revealed that susceptible mice harbored a different microbiome with a significant increase in the abundance of the bacterial genus Helicobacter. The introduction of H. hepaticus to the gut of nonsusceptible mice was sufficient to drive macrophage expansion and MZ B cell development. Given that myeloid cells and MZ B cells are part of the first line of defense against blood-borne-pathogens, their increase following a breach in the gut epithelial barrier would be protective. Thus IL-10 is an essential gatekeeper that maintains immune homeostasis at distal sites that can become functionally imbalanced upon the introduction of specific pathogenic bacteria to the intestinal track.

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“…37 Under normal circumstances, MZ B-cell precursors and MZ B cells are thought to compete for the interaction with limited Dll1 ligands, expressed on endothelial cells in the splenic red pulp. 31,38 The independency of the Dll1 ligand interaction by Notch2IC expression may enable the dramatic enlargement of the MZ, which has not been observed in any other mutant mouse strain before. Moreover, this ligand independency might allow the occurrence of MZ-like B cells in the lymph node, which may arise from either transitional or Fo B cells on initiated Notch2IC expression.…”

Section: Org Frommentioning

confidence: 99%