CXCL13 blockade disrupts B lymphocyte organization in tertiary lymphoid structures without altering B cell receptor bias or preventing diabetes in nonobese diabetic mice.
Lymphocytes that invade nonlymphoid tissues often organize into follicle-like structures known as tertiary lymphoid organs (TLOs). These structures resemble those found in spleen or lymph nodes, but their function is unknown. TLOs are recognized in many autoimmune diseases, including the NOD mouse model of type 1 diabetes. In some cases, TLOs have been associated with the B lymphocyte chemoattractant, CXCL13. Studies presented in this article show that CXCL13 is present in inflamed islets of NOD mice. Ab blockade of this chemokine unraveled B lymphocyte organization in islet TLOs, without reducing their proportion in the islets. These chaotic milieus contained B lymphocytes with the same distinct repertoire of B cell receptors as those found in mice with well-organized structures. Somatic hypermutation, associated with T-B interactions, was not impaired in these disorganized insulitis lesions. Finally, loss of B lymphocyte organization in islets did not provide disease protection. Thus, B lymphocytes infiltrating islets in NOD mice do not require the morphology of secondary lymphoid tissues to support their role in disease.
Henry
Rachel A
RA
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Kendall
Peggy L
PL
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D054382:Chemokine CXCL13 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D018450:Disease Progression; D005260:Female; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008221:Lymphoid Tissue / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D009924:Organ Culture Techniques; D010179:Pancreas / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D054380:Receptors, CXCR5 / Q000378:metabolism
C513179:CXCR5 protein, mouse; D054382:Chemokine CXCL13; C486386:Cxcl13 protein, mouse; D018836:Inflammation Mediators; D011947:Receptors, Antigen, B-Cell; D054380:Receptors, CXCR5