Disruption of the Bcl6 Gene Results in an Impaired Germinal Center Formation

Abstract

The Bcl6 gene has been identified from the chromosomal translocation breakpoint in B cell lymphomas, and its products are expressed highly in germinal center (GC) B cells. To investigate the function of Bcl6 in lymphocytes, we have generated RAG1-deficient mice reconstituted with bone marrow cells from Bcl6-deficient mice (Bcl6−/−RM). Lymphogenesis in primary lymphoid tissues of Bcl6−/−RM is normal, and Bcl6−/−RM produced control levels of primary IgG1 antibodies specific to T cell–dependent antigens. However, GCs were not found in these mice. This defect was mainly due to the abnormalities of B cells. Therefore, Bcl6 is essential for the differentiation of GC B cells.

Defect of CD8+ Memory T Cells Developed in Absence of IL-12 Priming for Secondary Expansion

“…For example, rapid responses to external stimuli are facilitated by the organization of signaling molecules downstream of the TCR in distinct lipid rafts (15) leading to impairment of further stimulatory responses. Bcl-6 is essential for memory B cell development in germinal center (16). It has recently been demonstrated that Bcl-6 also plays a role in generation and maintenance of CD8 + Tm cells induced in responses to Ag stimulation (17).…”

Alternate pathways for Bcl6‐mediated regulation of B cell to plasma cell differentiation

“…The transcription factor Bcl6 has been demonstrated to be essential for GC B-cell development, as Bcl6 knockout mice fail to develop GCs and do not produce high-affinity antibodies [7][8][9]. Recent work revealed that Bcl6 is also needed for follicular T helper cell development [10][11][12].…”

“…Furthermore, B-cell receptor (BCR) signaling of sufficient affinity leads to rapid phosphorylation and degradation of Bcl6 protein [5], while Bcl6 can also be functionally inactivated by acetylation [6]. These features of Bcl6 make it a prominent molecular trigger that controls the plasma cell differentiation.The transcription factor Bcl6 has been demonstrated to be essential for GC B-cell development, as Bcl6 knockout mice fail to develop GCs and do not produce high-affinity antibodies [7][8][9]. Recent work revealed that Bcl6 is also needed for follicular T helper cell development [10][11][12].…”

The proto-oncogene Bcl6 inhibits apoptotic cell death in differentiation-induced mouse myogenic cells

“…In human and murine lymphoid tissues, Bcl6 is preferentially expressed in B cells of the germinal center and in their neoplastic counterparts, including follicular, Burkitt's and di use large cell lymphomas (Cattoretti et al, 1995;Onizuka et al, 1995). The importance of Bcl6 in lymphoid tissues is supported by recent ®ndings that germinal center formation is impaired in Bcl6-de®cient mice (Dent et al, 1997;Fukuda et al, 1997;Ye et al, 1997). However, actual function of Bcl6 in the lymphomagenesis as well as the formation of germinal center still remain unclear.…”