germinal center response

spleen, lymph nodes, tonsil

circulating naiive CD4+ T cell first recognizes APC in an antigen non-specific fashion via adhesion molecules; interactions stabilized by recognition of processed antigen on surface of APC by T cell

recognize peptide antigen bound to MHC-2 on APC and receive co-stim signal from same cell

CD28 on T cell interacting w/ B7 on APC; co-stim signal makes IL-2 which is needed for T cell proliferation

once interacted w/ IL-2 can become TH cells via IL-4

follicular B cells must recognize antigen to move to T zone of secondary lymphoid organ; directed by CCL19 and CCL21

T cell zone of secondary lymphoid organ

TCR on TH2 cells; CD4 stabilize adhesion

TH cells and B cell must recognize epitopes of same molecular complex to interact

• signal 1: Ag/Ab interaction
• signal 2: co-stimulatory signals provided by IL-4 (from TH2 cell) and interaction between CD40 ligand (TH2 cell) and CD40 on B cell

*TH2 already activated by this point

CD40 ligand deficiency (from TH2 cell)

• 1. differentiate/proliferate into plasma cells that secrete IgM
• 2. activated B cells and TH2 migrate into follicle; B cells (aka centroblasts) divide rapidly and form a dark zone in the germinal center

rapidly dividing centroblasts and TH2 cells

centrocytes (non dividing); FDCs

isotype switching, somatic hypermutation

centrocyte Ag receptors interact w/ Ag on surface of FDC in light zone of germinal center; facilitates high affinity Ag-specific B cells

• 1. differentiate into plasma cells
• 2. return to resting state to become memory cells

bacterial polysaccharides, polymeric prot, lipopolysaccharides

substance w/ an intrinsic activity that can activate B cells indep of interaction w/ Ag receptor

i.e. TI-1

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

mechanism unknown

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

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

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

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

btw switch regions (highly repetitive DNA) in heavy chain gene

deletional somatic recombination

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

still converts C to U in switch region to create a base mismatch and initiate recombination process

AID---(C to U)---> UNG---- (U to abasic)---> APE 1---ss knicks ---> DNA-Pk---staggered DS breaks ---> ---> DSBR machinery ---> class switch recombination

induces IgG1-IgE

induces IgG2a-IgG3

IgG2b-IgA