| Introduction: IgA Nephropathy is the most common nephritis worldwide. Few treatments are available and disease etiology remains unclear, although APRIL has been implicated. BAFF-transgenic (-tg) mice require a microbiome to initiate disease, and these mice exhibit intestinal hyperplasia of Plasma Cells (PC) and hyperproduce IgA. I hypothesize that B cells that encounter antigens in the gut can egress from the gut and may potentially influence disease pathology.;Methods: ELISAs were used to measure BAFF/APRIL and commensal-specific antibodies in the periphery of BAFF-tg mice and human IgAN patients. PC migratory ability was tested via: (1) dual infection of Rotavirus (RV) and Influenza PR8 (flu), or experimental autoimmune encephalomyelitis (EAE); (2) RV infection and parabiosis; and (3) intestinal photoconversion in Kaede mice. RV-specific PC were measured in (1) and (2) in distal tissues via ELISPOT. BAFF-tg immune response to flu was measured through survival, viral titres, and inducible bronchus associated lymphoid tissue (iBALT) formation.;Results: Anti-commensal antibodies were found in BAFF-tg serum and kidneys as well as in human serum both in healthy controls and IgAN patients. RV-specific IgA+ PC can migrate from the intestine to distal tissues, including the lung during flu and homeostatically, and to the CNS after the peak of EAE disease in both BAFF-tg and WT mice. RV-specific IgA+ PC can also migrate from one parabiont to another after 30 days. In Kaede mice, photoconverted cells migrate to the lungs during flu and homeostatically. BAFF-tg mice had an enhanced immune response to flu infection, generating iBALT 4 days earlier than WT mice. However, this did not exacerbate renal disease or alter the viral load.;Conclusions: In WT mice, B cells primed in the intestine can migrate to distal tissues during inflammation and to the lungs homeostatically. However, only BAFF-tg mice had anti-commensal antibodies in their serum. While BAFF-tg mice generated an enhanced immune response to flu, this did not exacerbate renal pathology or change the viral load. Further studies are required to ascertain the implication of gut immunity entering the periphery, the function of these migrating PC and the impact this may have in a chronic disease setting. |
