A Coordinated Change in Chemokine Responsiveness Guides Plasma Cell Movements

By D. Hargreaves, P. Hyman, T. Lu, Vu N. Ngo, Afshin Bidgol, G. Suzuki, Y. Zou, Dan R. Littman, J. Cyster. Journal of Experimental Medicine, 2001

727 citations recorded by the source corpus.

Antibody-secreting plasma cells are nonrecirculatory and lodge in splenic red pulp, lymph node medullary cords, and bone marrow. The factors that regulate plasma cell localization are poorly defined. Here we demonstrate that, compared with their B cell precursors, plasma cells exhibit increased chemotactic sensitivity to the CXCR4 ligand CXCL12. At the same time, they downregulate CXCR5 and CCR7 and have reduced responsiveness to the B and T zone chemokines CXCL13, CCL19, and CCL21. We demonstrate that CXCL12 is expressed within splenic red pulp and lymph node medullary cords as well as in bone marrow. In chimeric mice reconstituted with CXCR4-deficient fetal liver cells, plasma cells are mislocalized in the spleen, found in elevated numbers in blood, and fail to accumulate normally in the bone marrow. Our findings indicate that as B cells differentiate into plasma cells they undergo a coordinated change in chemokine responsiveness that regulates their movements in secondary lymphoid organs and promotes lodgment within the bone marrow.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/18dc58a61c87a3d66db41e9e06c6efe414ac29be

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. J. Cyster
2. A. Luster
3. Eric G. Pamer
4. R. Förster
5. R. Lesley
6. K. Ansel
7. R. Mebius
8. Carola G. Vinuesa

In Oncology

1. J. Cyster
2. A. Luster
3. Eric G. Pamer
4. R. Mebius
5. N. Serbina

Citations in the corpus

• Differing Activities of Homeostatic Chemokines CCL19, CCL21, and CXCL12 in Lymphocyte and Dendritic Cell Recruitment and Lymphoid Neogenesis1 (2002, background): “Recently, CXCR4-deficient plasma cells were shown to localize aberrantly in the spleen and failed to accumulate appropriately in the bone marrow (31).”
• Orchestrating the orchestrators: chemokines in control of T cell traffic (2008, background): “Although it is most highly expressed in the lymph node medulla and in the vicinity of germinal centers, probably by local stromal cells, some CXCL12 is also detectable in the T cell are”
• Current understanding of stem cell mobilization: the roles of chemokines, proteolytic enzymes, adhesion molecules, cytokines, and stromal cells. (2002, background): “However, stem cell self-renewal, retention of maturing hematopoietic cells within the bone marrow, and migration patterns of both myeloid and lymphoid progenitor cells, including thymic T-cell development, were defective [30,32,33].”
• Germinal center dark and light zone organization is mediated by CXCR4 and CXCR5 (2004, background): “SDF-1 expression in the dark zone SDF-1 mRNA expression has been detected by in situ hybridization in the splenic red pul”
• Balanced responsiveness to chemoattractants from adjacent zones determines B-cell position (2002, background): “The CCL19-Fc recombinant protein was a fusion of mouse CCL19 and the human IgG1 constant regio”
• Extrafollicular antibody responses (2003, background): “Migration of B cells that have bound antigen to the T zone may in part be a consequence of their increased expression of CCR7, which ligates the T-zone chemokines CCL19 and CCL21 (40).”
• Regulation of plasma-cell development (2005, background): “Reduced expression of CXC-chemokine receptor 5 (CXCR5) and CC-chemokine receptor 7 (CCR7) causes plasma cells to have decreased responsiveness to the B-cell-zone and T-cell-zone chemokines CXCL13, CC-chemokine ligand 19 (CCL19) and CCL21 (Ref”
• Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2 (2006, background): “In contrast, plasma cells downregulate CCR7 and CXCR5 and have increased responsiveness to SDF-1 (ref”