substance w/ an intrinsic activity that can activate B cells indep of interaction w/ Ag receptor
can activate B cells through heavy BCR crosslinking of Ab on surface of B cell; this delivers both signal 1 and 2
over immune response, strength of Ab produced are changing and getting stronger
mech by which additional diversification of entire variable region of Ab occurs after the mature follicular B cell encounters Ag
req Ag, T cell help, in germinal center, AID protein
used in somatic hypermutation; converts C to U in DNA of V region and initiates mutation process
What does AID create?
mismatch (transition mutation)
OR UNG prot removes U to make abasic site (which can be knicked out and converted further into a transversion mutation
same set of antigenic determinants in the Fc of the heavy chains of the same class are the same
Heavy chain isotype switching
activated B cells in dk zone of germinal center of secondary lymphoid organ can switch from expression of IgM and IgD to expression of other heavy chain classes by asoc w/ rearranged VH gene segment w/ other heavy chain constant region (CH) genes
What is the significance of CH genes encoding Fc region of the Ab in isotype switching?
isotype switching allows B cells to produce Ab w/ other effector functions while maintaining specificity for immunizing Ag
second type of somatic recombination event in activated mature B cell; brings assembled VDJ exon into close proximity w/ another CH gene
Where does switch recombination occur?
btw switch regions (highly repetitive DNA) in heavy chain gene
What is another name for switch recombination?
deletional somatic recombination
How does switch recombination work?
signal induces two switch regions to come together and become ligated; intervening DNA is looped out and cut away; switch regions are in introns so reading frame is not messed up
How does AID work in switch recombination?
still converts C to U in switch region to create a base mismatch and initiate recombination process
What is the recombination process?
AID---(C to U)---> UNG---- (U to abasic)---> APE 1---ss knicks ---> DNA-Pk---staggered DS breaks ---> ---> DSBR machinery ---> class switch recombination
How does IL-4 play a role in isotype switching?
How does IFN-gamma play a role in isotype switching?
How does TGF-beta play a role in isotype switching?