lecture 6- the B cell response Flashcards
B cells express chemokine _____ unlike T cells and APCs that express chemokine ____.
CXCR5
CCR7
Where does CXCR5 chemokine lead the B cell displaying the correct receptor?
Follicles of the peripheral lymphoid organs
What do follicular dendritic cells do?
the present antigen coated in C3d or C3b and present them to B cells
What are the 2 ways a naïve B cell can be activated once it comes into contact with an antigen it can bind to
(1) BCR binds antigen, and coreceptor CR2 of Bcell binds C3d of antigen
(2) BCR binds antigen, and TLR binds PAMP of antigen
what does CD19 do?
CR2, which is a coreceptor for BCR, does not have an intracellular signaling domain. CR2 works with CD19 because CD19 does have a intracellular signaling domain
What is the general difference between a T-dependent antigen and a T-independent antigen?
T-dep needs Tcells to induce antibody response in B cell, whereas in T-independent, B cells induce antibody response without Tcell assistance
Describe B cell activation by antigens in a T-dependent manner [PART1: from follicle to interfollicular zone)
Follicular Dendritic Cells (FDCs) in the follicles of peripheral lymph organs present antigen to B cell. BCR+CR2(or TLR) bind antigen and antigen is endocytosed. Increase in MHCII and CCR7 receptors. CCR7 upregulation brings Bcell to interfollicular zone with T cells.
B’s MHCII binds CD4 and TCR or Tcell. B7 is upreg in B and CD28 in T which binds and causes stable binding. This tight binding allows for T cell to secrete cytokine to B cell, upregulating CXCR5
Describe B cell activation by antigens in a T-dependent manner [PART2: from interfollicular zone back to follicle]
The tight binding of Tcell to Bcell in the interfollicular zone lead to upregulation of CXCR5 causing the Bcell to go back to the follicular zone, bringing the T cell (now Tfh with it) With input now from FDC and Tfh the Bcell makes a germinal center in the follicular zone where there is proliferation of Bcell
Difference between primary and secondary follicles?
secondary follicles have germinal center.
What 3 things happen in germinal centers during B cell differentiation?
Constant low level secretion of antibodies which aids (1) Ig class switching from IgM to IgG, IgA or IgE; (2) somatic hypermutation / affinity maturation; and (3)generation of memory B cells.
What was the point of bringing back the helper T cell to the follicular zone? what is it doing anyways?
Tfh cells express CD40 ligand (CD40L) which engage the CD40 receptor B cells. Tfh cells also secrete cytokines. This leads to expression of the enzyme activation-induced deaminase (AID), which is required for both Ig class switching and somatic hypermutation.
What is Ig class switching
heavy (H) chain constant (C) region IS SWITCHED while retaining variable regions (the same antigen specificity). Different Ig isotypes have different effector functions so it can get more variety of microbes
How does the Ig class switching happen on a biochemical level?
there is deletion of DNA right before the C(mu) gene until right before the new heavy chain (basically taking out part of the old heavy chain while keeping VDJ).
CD40 on B cells with CD40L on Tfh cells
and different cytokines direct switching
For each class of Immunoglobulin which cytokine is needed?
IFN-γ (from Th1 cells) for IgG
IL4 (from Th2 cells) for IgE
IL-5 (from Th2 cells) or TGF-β for IgA
What is Hyper IgM syndrome?
is an immunodeficiency disease caused by defective expression of CD40L on TH cells, which prevents them from providing help to B cells for Ig class switching, resulting in high levels of IgM in the blood. The reduced levels of IgG and other non-IgM antibodies to microbial antigens results in greatly reduced elimination of microbes, and predisposes to pyogenic infections(Pus)
