Lecture #7 Flashcards
B cell maturation in the bone marrow
- Gene rearrangment 2. Junctional diversity 3. Negative selection Binding of BCR to a self molecule can result in elimination of the B cell or receptor editing
Receptor editing is done by
Reactivation of RAG1/2 genes
BCR can be either ____ or _____
IgM or IgD
Two possible B cell responses
DT (T dependent) The Ag is a peptide, requires Th cell, occurs in germinal centers of lymphoid follicles and produces IgA,G,E
TI (T independent) The Ag can be peptide, lipid, polysaccharide, nucleic acid, Th is not needed, occurs either in lymphoid organs or mucosal surfaces and produces only IgM
TD B cell activation
Requires 3 signals 1. Ag binding to BCR 2. CD40-CD40L binding between Th2 and the B cell 3. IL4,6 secreted from Th2
Upon activation B cells wil secrete ____ at first for
approx. ____ days
And migrate to _____________ interacting with _______ to induce
__________(4)
IgM
10
Cortical greminal center
fTh cells
Class switching
Proliferation
Affinity maturation
Memory
What activates fTh cells?
fDC secreting IL6
Affinity maturation
Or somatic hypermutation
Changing of the AA at the tip of the Ab in order to create stonger binding between the Ag and the Ab
Totally random process that may result in a lower affinity binding as well but only the high affinity Abs are chosen by the fDC FcR and by C3b CR3 binding
Class switching is cytokine dependent which cytokines induce which class?
INF gamma - IgG
IL5 - IgA
IL4/13 - IgE
AID
Activation induced deaminase
Another method in order to increase variability, AID converts cytidine to uracil at switch regions in the DNA, U is not a normal nucleotide in the DNA therefore repair system will be activated and random nucleotides will be inserted instead.
Differentiation of plasma cells to memory cells
Plasma cells that were activated by TD mechanism will migrate to the bone marrow to interact with stromal cells
Their interaction will produce long live memory cells by IL6 IL6R interaction, BAFF BCMA interactions and many more
Negative costimulation
If enough Ab were produced against a certain Ag, co binding of BCR with another epitope on the Ag and Fc region of a preformed Ab with Fc gamma RIIB will inhibit the B cell from producing more Ab
TI1 (B2 cells)
At high Ag conc polyclonal plasma cells are produced
At low Ag conc monoclonal plasma cells are produced
TI2 (B1cell)
Marginal zone B cells
Activated by polysaccharide Ag and cytokines secreted from DCs mainlt IL5
Produce pentameric IgM and also IgA