Inter-cellular signaling by cytokines between
B-cells, T- cells, and effector cells
B cell activation
A key
part of the immune system is the production of immunoglobulins (antibodies) by
B cells to bind and inactivate specific foreign antigens. The body produces B
cells with a wide range of antigen specificities in the immunoglobulin B cell
receptor, one antigen specificity per cell. When the B cell receptor
immunoglobulin binds antigen, that cell is activated to proliferate and create
plasma cells secreting immunoglobulins to bind that specific antigen. B cell
activation also creates memory cells with the same antigen specificity that do
not actively secrete immunoglobulin but provide for rapid future immune
responses to the same antigen.
B cells are not activated by antigen on their own, but require interaction with helper CD4+ T cells to become activated and proliferate. The B cell first expresses immunoglobulin on the cell surface as the B cell receptor. If the B cell receptor immunoglobulin binds specific antigen, then the cell internalizes the antigen and presents it to T cells in MHC II, where it is recognized by the T cell receptor. In addition to the interaction between the T cell receptor and the B cell MHC-antigen, T cell interaction with the B cell involves additional positive and negative regulatory signals. CD40 interaction with CD40L and CD28 interaction with CD80 provide positive costimulatory signals that stimulate B cell activation and proliferation. T cell receptor activation induces expression of molecules like the CD40 ligand that modulate the B cell-T cell interaction. The CD40-CD40L interaction induces cytokine production and expression of other genes and alters the fate of the B cell involved in the interaction. If the interaction between CD40 and CD40L is prolonged, the B cell can be induced to become a memory cell rather than a plasma cell. Fas ligand binding to Fas between B and T cells may negatively modulate B cell activation, inducing apoptosis that limits B cell proliferation and activation. Cytokines like IL-2, IL-4 and IL-10 also play an important role in B cell activation.
B cells are not activated by antigen on their own, but require interaction with helper CD4+ T cells to become activated and proliferate. The B cell first expresses immunoglobulin on the cell surface as the B cell receptor. If the B cell receptor immunoglobulin binds specific antigen, then the cell internalizes the antigen and presents it to T cells in MHC II, where it is recognized by the T cell receptor. In addition to the interaction between the T cell receptor and the B cell MHC-antigen, T cell interaction with the B cell involves additional positive and negative regulatory signals. CD40 interaction with CD40L and CD28 interaction with CD80 provide positive costimulatory signals that stimulate B cell activation and proliferation. T cell receptor activation induces expression of molecules like the CD40 ligand that modulate the B cell-T cell interaction. The CD40-CD40L interaction induces cytokine production and expression of other genes and alters the fate of the B cell involved in the interaction. If the interaction between CD40 and CD40L is prolonged, the B cell can be induced to become a memory cell rather than a plasma cell. Fas ligand binding to Fas between B and T cells may negatively modulate B cell activation, inducing apoptosis that limits B cell proliferation and activation. Cytokines like IL-2, IL-4 and IL-10 also play an important role in B cell activation.
T cell activation
T
helper cells play an essential role coordinating the activities of other parts
of the immune system, including B cells, cytotoxic T cells, macrophages and
other cells. The crucial nature of helper T cells in the normal immune response
is demonstrated by the severe immune deficiency associated with the HIV-induced
helper T cell depletion. To communicate with other cells, helper T cells
express a range of cell surface molecules, a few of which are illustrated in
this figure. Like all T cells, helper T cells express T cell receptors
complexed with the CD3 proteins that are responsible for the recognition and
response of the cell to specific antigens (see “T Cell Receptor Signaling
Pathway”). CD4 is commonly used as a marker for helper T cells, in contrast to
cytotoxic T cells, which express CD8. CD4 is used by HIV to gain cell entry, as
well as the CCR5 chemokine receptor. Thy1 provides a more general cell surface
antigen used to identify both T helper and cytotoxic T cells. CD28 provides a
costimulatory signal in association with the activation of the T cell receptor
complex by an antigen presenting cell that is required for the T cell to become
activated (see “The Co-Stimulatory Signal during T-cell Activation” pathway).
Adhesion molecules on the surface of T cells assist in their interaction with
other cells. LFA-1 binds to its ligand ICAM-1 in a variety of cells and T cells
themselves also express ICAM-1. The CD45 protein tyrosine phosphatase
dephosphorylates factors in the pathways involved in B cells and T cells
activation. Although CD45 is required for T cell receptor activation, exclusion
of CD45 from the local membrane region near the T cell receptor appears
important for efficient T cell activation. Helper T cells can be subdivided
further into Th1 and Th2 cells, distinguished by their response to different
antigens, differing cytokine expression and expression of different chemokine
receptors (see “Selective expression of chemokine receptors during T-cell
polarization”) CD2 is required for efficient helper T cell maturation and
stimulates their differentiation, but does not select for a specific increase
in Th1 or Th2 populations of cells.
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