Decreased expression of bone marrow extracellular matrix components and increases in the output of B cells in cathepsin-L mutant mice

G CAMICIA; M RICARDI; G LOMBARDI; H COSTA; J MUNDIÑANO; D LORENZO; G CABRERA; R MEISS; I PIAZZON; I NEPOMNASCHY

Río de Janeiro, Brasil

Congreso; ImmunoRío 2007; 2007

Latin American Association for Immunology

CTSLnkt mice harbor a mutation in the cathepsin L gene that induces early impairments in the intrathymic positive selection of CD4+ T cells.  We have previously shown that lymph nodes are hypertrophied  with  a 2- to 3-fold increase in the number of  CD8+ T and B220+  cells and, correlatively,  extracellular matrix components (ECM)   were also increased (J.Immunol.2005, 174: 7022–7032).  Bone marrow histology and FACS analysis showed higher numbers of bone marrow cells and increased daily output of B220+ cells, with no alterations in the percentages of the B cell precursor populations based on the analysis of B220, IgM, CD43, c-Myc and CD19 expression. Levels of epression of BM  fibronectin, laminin, and collagen type I and IV were clearly decreased as shown by inmunohistochemistry and Western blot techniques. In vivo, the absence of CTSL activity results in a deficient T-cell-dependent B-cell response, as determined by the significantly lower titles of IgG1 (58% reduction) and IgG2a (88% reduction) obtained on a secondary stimulation with OVA in incomplete Freund´s adjuvant, with a polarization to the Th2 phenotype. Alterations in T helper cell activity could account for these results. However, normal titers of IgG3 were detected in response to the T-independent NP-Ficoll antigen, in spite of   the increased numbers of B cells, suggesting that decreases in NK activity may be involved. These results indicate that CTSL nkt mutation broadly affects the immune system, influencing both the T and B cell compartments.