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Composite low grade lymphoma with two subpopulations in a same site is uncommon. We herewith report the case of an 80-year-old woman who presented with isolated bilateral dacryoadenomegaly. Pathological examination of an incisional biopsy of her right lacrimal gland was consistent with a marginal zone lymphoma. Flow cytometry immunophenotyping showed two distinct clonal B-cell populations expressing sIg D lambda or sIg M kappa restriction in the lacrimal gland, blood, and bone marrow. Both B-cells populations were sorted from peripheral blood for molecular biology investigations and comparison with molecular data performed on tumor and bone marrow cells. IgH PCR performed on purified blood populations disclosed two monoclonal peaks: 98 bp-sized peak in the sIg M kappa and a 107 bp in the sIg D lambda clones, respectively. The lacrimal gland tumor expressed mainly sIg M kappa population, and showed a major 98 bp-sized peak coexisting with a very minor 107 bp peak. Cytogenetic studies showed a 46, XX,del (7) (q22q32) karyotype. Bone marrow examination at diagnosis revealed the same B-cell clones distribution than the one observed in blood with a dominant sIg D lambda population, a Genescan profile showing a major peak of 107 bp and a minor peak of 98 bp. Chromosomal analysis disclosed a 46,XX,del (10) (?p14) karyotype without detectable 7q deletion. To our knowledge, this observation represents the first reported case of biclonal low grade lymphoma hidden behind a normal classical kappa/lambda Ig light chain ratio in blood, but clearly demonstrated by the combination of three ancillary techniques (flow cytometry both analytical and cell sorting, molecular biology, and cytogenetics) and analysis of different tissues (i.e., in this case, lacrimal gland biopsy, blood, and bone marrow)., ((c) 2007 Wiley-Liss, Inc.)

Toll-like receptor (TLR)-4 signaling pathway plays an essential role in host defense against gram-negative bacteria while TLR-3-mediated signaling is critically involved in anti-viral immunity. To gain insight into the defects responsible for impaired Th1 responses in human newborns, we investigated the responses of human cord blood cells to lipopolysaccharide, LPS, and to polyinosinic-polycytidylic acid, Poly (I:C), ligands of TLR-4 and TLR-3, respectively. Measurement of cytokine levels revealed a profound defect in IL-12 (p70) synthesis and an increased release of IL-10 in cord blood exposed to LPS or Poly (I:C), as compared to adult blood. Moreover, Poly (I:C)-induced IFN-alpha production was found to be significantly impaired in cord blood. Phenotypic maturation of myeloid DC in response to LPS or Poly (I:C) was next compared in cord and adult blood. We observed that neonatal myeloid DC displayed decreased upregulation of CD40, CD80 whereas CD86 and HLA-DR upregulation did not differ significantly between adults and neonates. Taken together, these findings might be relevant to the increased vulnerability of human newborns to intracellular pathogens and to their inability to develop efficient Th1-type responses.

It was observed that interferon beta (IFN-beta) prevents the down-regulation of the interleukin-3 receptor alpha chain (IL-3Ralpha), which spontaneously occurs during culture of human monocytes. The functionality of IL-3R was demonstrated by the fact that IL-3 rescued IFN-beta-treated monocytes from apoptosis. Monocytes cultured in the presence of IFN-beta and IL-3 acquire a dendritic morphology and express high levels of HLA antigen class I and class II and costimulatory molecules. When stimulated by either lipopolysaccharide or fibroblasts expressing CD40 ligand (CD40L) transfectants, dendritic cells (DCs) generated in IFN-beta and IL-3 secreted high levels of IL-6, IL-8, and tumor necrosis factor-alpha but low levels of IL-12 in comparison with DCs generated in IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF). In mixed leukocyte culture, IL-3-IFN-beta DCs induced a vigorous proliferative response of allogeneic cord blood T cells and elicited the production of high levels of IFN-gamma and IL-5 by naive adult CD4+ T cells. Finally, IL-3-IFN-beta DCs were found to produce much higher levels of IFN-alpha than IL-4-GM-CSF DCs in response to Poly (I:C) but not to influenza virus. It was concluded that monocytes cultured in the presence of IL-3 and IFN-beta differentiate into DCs with potent helper T-cell stimulatory capacity despite their low secretion of IL-12.