immuno 11 B cell activation 2 Flashcards
What happens when T cells bind B cells?
On activation, helper T cells express CD40 ligand (CD40L), which engages its receptor, CD40, on antigen-stimulated B cells at the T-B interface and induces subsequent proliferation and differentiation initially in extrafollicular foci and later in germinal centers
When do extrafollicular foci and germinal centers appear after an infection?
Extrafollicular foci of T-dependent B cell activation are generated relatively early in an immune response. Germinal centers, in which specialized follicular helper T (TFH) cells trigger B cells to undergo numerous changes, appear a few days later.
Each fully formed germinal center contains cells derived from only one or a few antigen specific B cell clones
What are some characteristic changes in B cells in response to T cell mediated activation?
affinity maturation, isotype switching, generation of memory B cells, and long-lived plasma cell differentiation, occur primarily in the germinal centers of lymphoid follicles.
How are cloned B-cells chosen from the germinal center?
FDCs express complement receptors (CR1, CR2, and CR3) and Fc receptors. These molecules are involved in displaying antigens for the selection of germinal center B cells.
B-cell clones with the best affinity survive.
What type of antibodies is produced in response to polysaccharide antigens?
IgM mainly, with sometimes a little IgG (no T-cell cytokine mediation for class switching)
What do TH1 helper cells produce and in response to what?
In response to viruses and bacteria.
Produce IFN gamma
What do TH2 helper cells produce and in response to what?
Helminths activate the TH2 subset of helper T cells, which produces IL-4, the cytokine that induces switching to IgE
What is affinity maturation?
the process that leads to increased affinity of antibodies for a particular antigen as a T-dependent humoral response progresses and is the result of somatic mutation of Ig genes followed by selective survival of the B cells producing the antibodies with the highest affinities.
mutations are clustered in the V regions, mostly in the antigen-binding complementarity-determining regions
What are the 2 types of plasma cells and how do they differ?
Short-lived plasma cells are generated during T-independent responses and early during T cell– dependent responses in extrafollicular B cell foci. These cells are generally found in secondary lymphoid organs and in peripheral nonlymphoid tissues
Long-lived plasma cells are generated in T-dependent germinal center responses to protein antigens. Signals from the B cell antigen receptor and IL-21 cooperate in the generation of plasma cells, acquire the ability to home to the bone marrow, where they are maintained by cytokines of the BAFF family
How are B-cell clones selected to leave the germinal center?
germinal center B cells migrate into the FDC-rich light zone of the germinal center. IL-21 secreted by TFH cells induces the expression of proteins that induce apoptosis and reduces the expression of proteins that prevent apoptosis. Therefore, these B cells die by apoptosis unless they are rescued by recognition of antigen. B cells with high-affinity receptors for the antigen are best able to bind the antigen when it is present at low concentrations, and these B cells survive preferentially because of several mechanisms
What are some phenotypical changes when B-cells differentiate?
the cell enlarges dramatically, and the ratio of cytoplasm to nucleus also undergoes a striking increase. The endoplasmic reticulum becomes prominent, and the cell is transformed into a secretory cell that bears little or no resemblance to a B cell.
Antibodies released by plasma cells are different than normal B-cell surface antibodies.
What are memory cells?
antigen-activated B cells emerging from germinal centers acquire the ability to survive for long periods (by expressing high levels of the antiapoptotic protein Bcl-2), apparently without continuing antigenic stimulation.
Release isotype-switched, high affinity antibodies with 2nd exposure.
Where do B memory cells reside?
Some memory B cells may remain in the lymphoid organ where they were generated, whereas others exit germinal centers and recirculate between the blood and lymphoid organs
What happens to memory cells after 2nd response?
After re-encountering the specific antigen they are able to reactivate very quickly, propagate themselves, create plasma cells and reenter germinal centres to improve affinity of their antibodies
How is B-cell proliferation halted?
Secreted antibodies inhibit continuing B cell activation by forming antigen-antibody complexes that simultaneously bind to antigen receptors and inhibitory Fcγ receptors on antigen-specific B cells
Secreted antibodies inhibit continuing B cell activation by forming antigen-antibody complexes that simultaneously bind to antigen receptors and inhibitory Fcγ receptors on antigen-specific B cells
