High B cell production rate in Cathepsin-L deficient mice”

BADANO N; CAMICIA G; MAGLIOCO A; PIAZZON I; NEPOMNASCHY I

Congreso; 9th Latin American Congress of Immunology; 2009

Cathepsin-L deficient (CTSLnkt/nkt) mice show increases in B lymphocytes number and in the extracellular matrix (ECM) components in lymph nodes (LN). In this study, we investigated the mechanisms involved in the high LN B cells number in CTSLnkt/nkt mice. Neither LN nor spleen showed alterations in in vivo basal B cells proliferative (5-bromo-2-deoxyuridine) and apoptosis (propidium iodide) levels in CTSLnkt/nkt mice. When the adhesion molecules that enable the entry of lymphocytes into the LN were studied, an increase in the percentage of LFA-Ihigh and CD44high in CD19+ cells was observed. To investigate the B-cell production by the bone marrow (BM) -which shows low levels of ECM glycoproteins in CTSLnkt/nkt mice- we performed colony-forming unit pre-B (CFU pre-B) assays in a methylcellulose and IL-7 supplemented medium. At day 7, the number of CTSLnkt/nkt BM CFU pre-B cells was significantly higher than the number of wild type BM CFU pre-B cells. These results suggest that the elevated LN B cells numbers in CTSLnkt/nktmice are, in part, a consequence of an increased B lymphopoiesis. We hypothesize that cathepsin-L -probably acting on the ECM composition- plays a role in the regulation of B cell production and their distribution in the peripheral lymphoid organs.