NF-kappaB is essential for the progression of KSHV- and EBV-infected lymphomas in vivo.

Activated NF-kappaB is a critical mechanism by which lymphoma cells infected by Epstein-Barr virus (EBV/HHV-4) and Kaposi sarcoma herpesvirus (KSHV/HHV-8) are protected from apoptotic stress. Selective pharmacologic inhibition of constitutive NF-kappaB activity induces apoptosis in KSHV- and EBV-infected lymphoma cells. In both tumor types, pharmacologic inhibition of NF-kappaB in vitro induced identical mitochondrially mediated apoptosis cascades.

Lymphoma B cells evade apoptosis through the TNF family members BAFF/BLyS and APRIL.

The mechanisms underlying the autonomous accumulation of malignant B cells remain elusive. We show in this study that non-Hodgkin's lymphoma (NHL) B cells express B cell-activating factor of the TNF family (BAFF) and a proliferation-inducing ligand (APRIL), two powerful B cell-activating molecules usually expressed by myeloid cells. In addition, NHL B cells express BAFF receptor, which binds BAFF, as well as transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and B cell maturation Ag (BCMA), which bind both BAFF and APRIL.

Inhibition of Fas-mediated apoptosis by antigen: implications for lymphomagenesis.

Apoptotic deletion of expanded B cell populations is essential in avoidance of autoimmune disease and immune regulation of some B cell malignancies. The role of CD4+ T cells in B cell apoptosis is evident from the high incidence of B cell tumors and autoimmunity in patients with T cell diseases such as the acquired immune deficiency syndrome (AIDS). We have previously demonstrated that in Epstein-Barr Virus (EBV) negative Burkitt's lymphoma (BL), a tumor derived from proliferating centroblasts of the germinal center, the malignant lymphocytes can be induced to express Fas (CD95) by ligation of CD40 at the B cell surface.

Ongoing in vivo immunoglobulin class switch DNA recombination in chronic lymphocytic leukemia B cells.

Chronic lymphocytic leukemia (CLL) results from the expansion of malignant CD5(+) B cells that usually express IgD and IgM. These leukemic cells can give rise in vivo to clonally related IgG(+) or IgA(+) elements. The requirements and modalities of this process remain elusive.

Apoptosis in lymphocytic leukemias and lymphomas.

Most current classifications of lymphoid neoplasms define the tumors based on the cell of origin, phenotype, genetic abnormalities, and clinical features. Here it is proposed that human lymphocytic tumors can be categorized based on the propensity and capacity of the tumor cells to undergo apoptosis. The first category is defined by malignant cells that are resistant to apoptosis due to expression of anti-apoptotic factors such as bcl-2 and cellular inhibitors of apoptosis (IAPs).

Germinal center B cells regulate their capability to present antigen by modulation of HLA-DO.

Peptide acquisition by MHC class II molecules is catalyzed by HLA-DM (DM). In B cells, HLA-DO (DO) inhibits or modifies the peptide exchange activity of DM. We show here that DO protein levels are modulated during B cell differentiation.