Early events of T cell activation monitored at the single cell level for depined numbers of class II MHC-antigen complexes borne by dendritic cells or by resting B cells

Effective T-cell activation requires antigen/major histocompatibility complex engagement by the T-cell receptor complex in concert with one or more costimulatory molecules. Recent studies have suggested that the B7 molecule, expressed on most antigen presenting cells, functions as a costimulatory molecule through its interaction with CD28 on T cells. Blocking the CD28/B7 interaction with CTLA4Ig inhibits T-cell activation in vitro and induces unresponsiveness. We demonstrate that another molecule(s), termed B7-2, is expressed constitutively on dendritic cells, is differentially regulated on B cells, and costimulates naive T cells responding to alloantigen. B7-2 is up-regulated by lipopolysaccharide in < 6 hr and is maximally expressed on the majority of B cells by 24 hr. In contrast, B7 is detected only on a subset of activated B cells late (48 hr) after stimulation. In addition, Con A directly induces B7-2 but not B7 expression on B cells. Finally, although both anti-B7 monoclonal antibodies and CTLA4Ig blocked T-cell proliferation to antigen-expressing B7 transfectants, only CTLA4Ig had any significant inhibitory effect on T-cell proliferation to antigens expressed on natural antigen presenting cells, such as dendritic cells. Thus, B7 is not the only costimulatory molecule capable of initiating T-cell responses since a second ligand, B7-2, can provide a necessary second signal for T-cell activation.

Download Full-text

Antigen-unspecific B Cells and Lymphoid Dendritic Cells Both Show Extensive Surface Expression of Processed Antigen–Major Histocompatibility Complex Class II Complexes after Soluble Protein Exposure In Vivo or In Vitro

Journal of Experimental Medicine ◽

10.1084/jem.186.5.673 ◽

1997 ◽

Vol 186 (5) ◽

pp. 673-682 ◽

Cited By ~ 97

Author(s):

Guangming Zhong ◽

Caetano Reis e Sousa ◽

Ronald N. Germain

Keyword(s):

Dendritic Cells ◽

Major Histocompatibility Complex ◽

T Cell ◽

B Cells ◽

Mhc Class Ii ◽

T Cell Activation ◽

Cell Activation ◽

Class Ii ◽

Histocompatibility Complex

Intravenous (i.v.) injection of high amounts of soluble proteins often results in the induction of antigen-specific tolerance or deviation to helper rather than inflammatory T cell immunity. It has been proposed that this outcome may be due to antigen presentation to T cells by a large cohort of poorly costimulatory or IL-12–deficient resting B cells lacking specific immunoglobulin receptors for the protein. However, previous studies using T cell activation in vitro to assess antigen display have failed to support this idea, showing evidence of specific peptide–major histocompatibility complex (MHC) class II ligand only on purified dendritic cells (DC) or antigen-specific B cells isolated from protein injected mice. Here we reexamine this question using a recently derived monoclonal antibody specific for the T cell receptor (TCR) ligand formed by the association of the 46-61 determinant of hen egg lysozyme (HEL) and the mouse MHC class II molecule I-Ak. In striking contrast to conclusions drawn from indirect T cell activation studies, this direct method of TCR ligand analysis shows that i.v. administration of HEL protein results in nearly all B cells in lymphoid tissues having substantial levels of HEL 46-61–Ak complexes on their surface. DC readily isolated from spleen also display this TCR ligand on their surface. Although the absolute number of displayed ligands is greater on such DC, the relative specific ligand expression compared to total MHC class II levels is similar or greater on B cells. These results demonstrate that in the absence of activating stimuli, both lymphoid DC and antigen-unspecific B cells present to a similar extent class II–associated peptides derived from soluble proteins in extracellular fluid. The numerical advantage of the TCR ligand–bearing B cells may permit them to interact first or more often with naive antigen-specific T cells, contributing to the induction of high-dose T cell tolerance or immune deviation.

Download Full-text

The minimal number of class II MHC-antigen complexes needed for T cell activation

Science ◽

10.1126/science.2118680 ◽

1990 ◽

Vol 249 (4972) ◽

pp. 1028-1030 ◽

Cited By ~ 285

Author(s):

S Demotz ◽

H. Grey ◽

A Sette

Keyword(s):

T Cell ◽

T Cell Activation ◽

Cell Activation ◽

Class Ii ◽

Class Ii Mhc ◽

Mhc Antigen

Download Full-text

Dendritic Cells Enhance Growth and Differentiation of CD40-activated B Lymphocytes

Journal of Experimental Medicine ◽

10.1084/jem.185.5.941 ◽

1997 ◽

Vol 185 (5) ◽

pp. 941-952 ◽

Cited By ~ 217

Author(s):

Bertrand Dubois ◽

Béatrice Vanbervliet ◽

Jérome Fayette ◽

Catherine Massacrier ◽

Cees Van Kooten ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

T Cell ◽

B Cells ◽

B Cell ◽

T Cell Activation ◽

Cell Activation ◽

Interleukin 2 ◽

Lymphoid Organs ◽

Secondary Lymphoid Organs

After antigen capture, dendritic cells (DC) migrate into T cell–rich areas of secondary lymphoid organs, where they induce T cell activation, that subsequently drives B cell activation. Here, we investigate whether DC, generated in vitro, can directly modulate B cell responses, using CD40L-transfected L cells as surrogate activated T cells. DC, through the production of soluble mediators, stimulated by 3- to 6-fold the proliferation and subsequent recovery of B cells. Furthermore, after CD40 ligation, DC enhanced by 30–300-fold the secretion of IgG and IgA by sIgD− B cells (essentially memory B cells). In the presence of DC, naive sIgD+ B cells produced, in response to interleukin-2, large amounts of IgM. Thus, in addition to activating naive T cells in the extrafollicular areas of secondary lymphoid organs, DC may directly modulate B cell growth and differentiation.

Download Full-text