L10, BCR and TCR expression Flashcards
what are the first steps to the generation of a functional BCR in developing B cells
recombination of heavy chain, D and J segments
what happens after the first round of recombination (D and J segments)?
recombination of V and DJ segments. if this is successful, there is no recombination in allele #2 and kappa rearrangement is thereby induced
what happens if second recombination of heavy chain is nonproductive with allele #1?
another recombination (V and DJ), but with allele #2 occurs. If productive, the micro heavy chain and the surrogate light chain form the pre-BCR and induces kappa rearrangement
what happens if recombination with allele #2 is nonproductive?
the cell undergoes apoptosis
what is the next step in BCR generation once a productive allele is used?
micro and kappa chains combine and inhibit rearrangement of kappa allele #2 and lambda rearrangement. the nonproductive allele does not combine with kappa chain - this forms the pre-BCR which can now allow recombination of light chain, lambda rearrangement occurs and so on until its unproductive…or death
what is allelic exclusion in B cells?
the mechanism by which a single heavy chain and a single light chain from only one of the alleles are transcribed and translated into proteins
what does the allelic exclusion in B cells contribute towards?
reduces the probabilities of generating auto-reactive BCR/antibodies … but is energetically expensive
if avidity of the BCR is moderate, …
development of B cells continues
what happens if avidity is high?
another round of light chain recombination can occur, known as receptor editing - this is a way of quality control that occurs in bone marrow
what happens if avidity remains high, despite light chain recombination?
cell death or anergy (lack of energy)
after BCR, stimulation of the B cells causes …
secretion of IgM (or IgD) anitbodies
what is class switching?
Ig class swithces due to additional DNA recombination = Class Switch Recombination (CSR)
what is affinity maturation?
when the binding strength of antibodies/BCR to antigens are “fine-tuned”/ small changes are made in the variable region - occurs by point mutations in the V genes = somatic hypermutation (SHM)
how does signal transduction work through BCRs?
upon binding with an antigen, BCR associates with Ig Superfamily members Ig-alpha and Ig-beta (also known as CD79a and CD79b). this generates intracellular signals though immunoreceptor Tyrosine-based Activation Motifs (ITAM) - leads to activation and changes in the B cell
what forms T-cell receptors (TCR)?
alpha and beta chains OR delta epsilon and sigma chains - the TCR is a membrane-bound heterodimer
how must antigen binding and recognition by TCR occur?
must occur through antigen presentation by the correct MHC (major histocompatibility complex) molecule = MHC restriction
where does allelic exclusion also occur?
T cells - TCR-beta chain, successful rearrangement of one beta allele prevents rearrangement of the second allele
what are the different types of MHC restriction?
two types of no recognition and “self restriction” (3 types total). self restriction is the result of a need for the TCR to properly engage both MHC and a specific antigenic peptide.
no recognition (1 & 2): inability to engage the MHC results in a failure to recognize the bound Ag, or it is the correct Ag with the wrong MHC class molecule
signal transduction through the TCR: like the BCR, the TCR has a short cytoplasmic tail that is ….
incapable of mediating intracellular signaling
what is TCR signaling facilitated by?
accessory molecules: CD3 - transmembrane proteins with ITAM motifs on their cytoplasmic tails
what is the role of co-receptors with TCR?
bind the invariant regions of the MHC molecules
1. CD4-MHCII (beta2 domain)
2. CD8-MHCI (alpha3 domain)
also act as markers to distinguish T Helper cells from Cytotoxic T cells (CD8+)
interacts with cytoplasmic tyrosine kinase Lck (signaling mediator)
increases sensitivity to the antigen a 100-fold
