3. HYPOGAMMAGLOBULINEMIA IN CHRONIC LYMPHOCYTIC LEUKEMIA (CLL): ROLE OF LEUKEMIC CELLS.

BERNATOWIEZ JULIANA; CASSARINO CHIARA; COLADO ANA; SARAPURA MARTINEZ VALERIA JUDITH; BUONINCONTRO BRENDA; BERTINI MARTIN; BEZARES RAIMUNDO FERNANDO; VERMEULEN MÓNICA; GAMBERALE ROMINA; BORGE MERCEDES; GIORDANO MIRTA

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias; 2022

Reunión Anual de Sociedades de Biociencias, Buenos Aires 16-19 Noviembre 2022.

Hypogammaglobulinemia (HGG) is a common immune deficiencyin CLL and can cause a high morbidity due to respiratory infections.In our cohort of patients from a single center we found that 14 of 29had IgG HGG and 10 of 29 had IgM HGG at diagnosis (IgG<700mg/dl; IgM<40 mg/dl). The precise mechanism responsible for HGGis unknown. The fact that HGG is present even at initial stages ofthe disease suggests that it cannot be attributed to infiltrative accumulationof clonal cells in the bone marrow. To gain insight into themechanisms involved in HGG, we took advantage of the CLL mousemodel Eu-TCL-1 that develops leukemia in aged mice. The leukemiccells from TCL-1 donors are usually transplanted into syngeneic wt(C57) mice to accelerate the disease course. We found that leukemicmice have significantly lower levels of IgG but not IgM in plasmacompared to control animals (IgG 1180 ± 0.08 versus 410 ± 0.05mg/dl; n=12; p<0.05, Mann Whitney test). To determine if leukemiccells impair the secretion IgG, we activated purified B cells from C57spleen (2x105/ml) with LPS (2.5 ug/ml) in the presence or not ofleukemic cells (1x105/ml) for 5 days. IgG levels in supernatants wereevaluated by ELISA. Our results show that co-culture of activated Bcells and leukemic cells significantly decreased IgG (B cells alone:12.31 ± 0.06 ng/ml; B cells in the presence of leukemic cells: 7.40 ±0.91 ng/ml, n= 5, p<0.05, Friedman test, followed by Dunn’s multiplecomparisons test). In addition we found that leukemic cells impairedthe proliferative capacity of B cells in response to LPS as measuredby the CFSE dilution assay and flow cytometry (% of proliferationof B cells alone 72.53 ± 0.97 vs % of proliferation of B cells in thepresence of leukemic cells 55.45 ± 3.02; p<0.05, Wilcoxon matchedpairssigned rank test). We conclude that malignant cells exert aninhibitory effect on B lymphocytes that might explain, at least in part,HGG in CLL.