INVESTIGADORES
MAGLIOCO Andrea Florencia
congresos y reuniones científicas
Título:
Increased bone marrow B cells export in CTSLnkt/nkt mice.
Autor/es:
BADANO N; CAMICIA G; MAGLIOCO A; MUNDIÑANO J; COSTA H; PIAZZON I; NEPOMNASCHY I
Reunión:
Congreso; First French-Argentine Immunology Congress; 2010
Resumen:
Cathepsin-L deficient mice (CTSLnkt/nkt) have alterations in
lymph node (LN) cellular composition including an increase in
B cells number. Besides, the levels of extracellular matrix components
are increased in the LN of CTSLnkt/nkt mice, whereas in
the bone marrow (BM) they are decreased. We previously demonstrated
that neither CTSLnkt/nkt LN nor spleen have alterations
in in vivo B cells basal proliferative and apoptosis levels.
Furthermore, we showed that although B cell development in
CTSLnkt/nkt BM is normal, CTSLnkt/nkt BM is able to produce
more B cells progenitors in vitro, being the BM stroma involved
in this increase. Taking into account these results, we hypothesized
that CTSLnkt/nkt BM might export higher B cells number
to the periphery. We measured by FACS the splenic transitional B
cells subset (HSAhiB220lo) which represents newly formed BMderived
B cells. We found signi*cant increased levels of transitional
B cells in CTSLnkt/nkt spleen (mean % HSAhiB220lo cells
± SD: 11.3 ± 2.2 in CTSLnkt/nkt mice vs 5.1 ± 0.9 in wild type (wt)
mice; n=4; p menor0.005). To confirm if a greater number of BM B cells
reach the CTSLnkt/nkt spleen, we injected mice with bromodeoxyuridine
(BrdU). Considering that pro-B and pre-B cells are
actively cycling cells and that most splenic B cells are quiescent,
a brief in vivo labeling pulse of BM precursors allowed us to
follow the fate of a cohort of newly generated B cells. Analysis
by FACS revealed an increase in the absolute numbers (AN) of
BrdU-labeled splenic B cells fractions I, II y III in CTSLnkt/nkt mice
(mean AN BrdU+cells x105 ± SD; n=4; FI: 4.9 ± 1.1 in CTSLnkt/nkt
mice vs 2.3 ± 0.9 in wt mice; p menor 0.01; FII: 8.0 ± 1.1 in CTSLnkt/nkt
mice vs 3.6 ± 1.2 in wt mice; p menor 0.005; FIII: 25.5 ± 3.9 in CTSLnkt/
nkt mice vs 14.8 ± 3.4 in wt mice; p menor 0.05). These results indicate
that CTSL deficiency increases both production and output of
BM B cells in CTSLnkt/nkt mice, probably as a consequence of
an abnormal BM microenvironment.