CD4+ T cells downregulate Bcl-2 in germinal centers.
Germinal centers (GCs) are the main site of T cell-dependent antibody responses. Upon antigen challenge, GCs comprise mostly B cells undergoing proliferation, somatic hypermutation and antigen-affinity selection. GC B cells down-modulate the expression of Bcl-2 protein and are highly sensitive to apoptosis to eliminate autoreactive or low-affinity cells. Bcl-2 is still expressed in a few GC cells, whose identity remains unclear. To address this issue, we examined by confocal microscopy the expression of Bcl-2 by different GC lymphocyte subsets in hyperplastic tonsils. We found that the vast majority of Bcl-2(+) GC cells are T lymphocytes. Conversely, while in the mantle zone and in the interfollicular areas T cells are almost exclusively Bcl-2(+), in the GC, most T lymphocytes are Bcl-2(-). In addition, most of the CD4(+) GC T cells are Bcl-2(-), while nearly 100% of the CD8(+) GC T cells are Bcl-2(+). The Bcl-2 downregulation by both B and CD4(+) T GC cells supports the concept that these two subsets may undergo a selection process in this microenvironment.
Schenka
André Almeida
AA
Department of Pathology and Inserm U563, Centre de Physiopathologie de Toulouse, Purpan, France. schenka@hotmail.com
Müller
Sabina
S
Fournié
Jean-Jacques
JJ
Capila
Florence
F
Vassallo
José
J
Delsol
Georges
G
Valitutti
Salvatore
S
Brousset
Pierre
P
D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry; D015536:Down-Regulation / Q000235:genetics; D018858:Germinal Center / Q000737:chemistry*; D006801:Humans; D016131:Lymphocyte Subsets / Q000737:chemistry; D018613:Microscopy, Confocal; D014066:Palatine Tonsil / Q000166:cytology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis* / Q000235:genetics
D019253:Proto-Oncogene Proteins c-bcl-2