The role of CD154 in haematopoietic development

2010 ◽  
Vol 104 (10) ◽  
pp. 639-701 ◽  
Author(s):  
Tom Seijkens ◽  
David Engel ◽  
Marc Tjwa ◽  
Esther Lutgens
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Activation ◽  
Cd40 Ligand ◽  
B Cell Activation ◽  
Genetic Studies ◽  
Therapeutic Implications ◽  
Lymphoid Malignancies ◽  
Stem And Progenitor Cells

SummaryCD154 (CD40 ligand, CD40L, gp139) is a co-stimulatory molecule of the tumour necrosis factor (TNF) family. CD154 was originally discovered on T-cells, and was found to be involved in many immune responses including B-cell activation, isotype switching, and germinal centre formation. The expression of CD154 on other haematopoietic and nonhaematopoietic cells suggests that CD154 has other functions as well. Indeed, CD154 is involved in many pathological processes, including inflammatory and autoimmune diseases. Genetic studies in patients and mice taught us that CD154 might affect haematopoietic stem and progenitor cells (HSPCs), T-cell, B-cell, and dendritic cell (DC) progenitors. Moreover, the development of specific T-cell and DC subsets critically depends on CD154. Furthermore, CD154 is involved in lymphoid malignancies. Here we highlight the role of CD154 in the developing lymphoid system, including the biology of HSPC and lineage-committed T-cell, B-cell, NK, and DC progenitors. Further, the clinical and therapeutic implications of CD154 interactions in lymphopoiesis will be discussed.

scholarly journals Antiviral Protection and Germinal Center Formation, But Impaired B Cell Memory in the Absence of CD19

1998 ◽  
Vol 188 (1) ◽  
pp. 145-155 ◽  
Author(s):  
Thomas Fehr ◽  
Robert C. Rickert ◽  
Bernhard Odermatt ◽  
Jürgen Roes ◽  
Klaus Rajewsky ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Cell Activation ◽  
Antibody Responses ◽  
B Cell Activation ◽  
Protein Antigens ◽  
Cell Memory ◽  
B Cell Memory

Coligation of CD19, a molecule expressed during all stages of B cell development except plasmacytes, lowers the threshold for B cell activation with anti-IgM by a factor of 100. The cytoplasmic tail of CD19 contains nine tyrosine residues as possible phosphorylation sites and is postulated to function as the signal transducing element for complement receptor (CR)2. Generation and analysis of CD19 gene–targeted mice revealed that T cell–dependent (TD) antibody responses to proteinaceous antigens were impaired, whereas those to T cell–independent (TI) type 2 antigens were normal or even augmented. These results are compatible with earlier complement depletion studies and the postulated function of CD19. To analyze the role of CD19 in antiviral antibody responses, we immunized CD19−/− mice with viral antigens of TI-1, TI-2, and TD type. The effect of CD19 on TI responses was more dependent on antigen dose and replicative capacity than on antigen type. CR blocking experiments confirmed the role of CD19 as B cell signal transducer for complement. In contrast to immunization with protein antigens, infection of CD19−/− mice with replicating virus led to generation of specific germinal centers, which persisted for >100 d, whereas maintenance of memory antibody titers as well as circulating memory B cells was fully dependent on CD19. Thus, our study confirms a costimulatory role of CD19 on B cells under limiting antigen conditions and indicates an important role for B cell memory.

scholarly journals Role of membrane immunoglobulin (Ig) crosslinking in membrane Ig-mediated, major histocompatibility-restricted T cell-B cell cooperation.

1985 ◽  
Vol 162 (5) ◽  
pp. 1695-1708 ◽  
Author(s):  
H P Tony ◽  
N E Phillips ◽  
D C Parker
Keyword(s):  
T Cell ◽  
B Cell ◽  
Antigen Presentation ◽  
T Cell Activation ◽  
Cell Activation ◽  
B Cell Activation ◽  
Major Histocompatibility ◽  
Class I Mhc ◽  
T Cell Help

Resting murine B lymphocytes can present rabbit anti-Ig to T cell lines specific for normal rabbit globulin. The T cell-B cell interaction is major histocompatibility complex (MHC)-restricted, and leads to activation, proliferation, and differentiation of the resting B cell into an antibody-secreting cell. Efficient antigen presentation and B cell activation depends upon binding of rabbit globulin to (membrane) mIg. To investigate the role of mIg in this polyclonal model for a T cell-dependent primary antibody response, we determined whether crosslinking of mIg is required either for efficient antigen presentation, as measured by helper T cell activation, or for the B cell response to T cell help, since all the direct effects of anti-Ig on B cells require crosslinking of mIg. We found that monovalent Fab' fragments of anti-IgM or anti-IgD work as efficiently as their divalent counterparts. Therefore, a signal transduced through the antigen receptor seems not to be required when T cell help is provided by an MHC-restricted T helper cell recognizing antigen on the B cell surface. Moreover, rabbit globulin bound to class I MHC molecules in the form of anti-H-2K also results in efficient antigen presentation and T cell-dependent B cell activation. However, mIg still appears to be specialized for antigen presentation, since anti-Ig is presented about three- to fivefold more efficiently than anti-H-2K.

scholarly journals Essential Role of IL-21 in B Cell Activation, Expansion, and Plasma Cell Generation during CD4+ T Cell-B Cell Collaboration

2007 ◽  
Vol 179 (9) ◽  
pp. 5886-5896 ◽  
Author(s):  
Stefan Kuchen ◽  
Rachel Robbins ◽  
Gary P. Sims ◽  
Chen Sheng ◽  
Terence M. Phillips ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Plasma Cell ◽  
Essential Role ◽  
Cell Activation ◽  
Cell Generation ◽  
Cd4 T Cell ◽  
B Cell Activation
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