B Lymphocyte Activation Flashcards
list and describe the 2 types of B cell responses
- T dependent: requires helper T cells and is the majority of B cell responses
- T independent: does not require helper T cells
what are two disadvantages of T independent B cell responses?
- not as strong or as specific response
2. does not yield memory cells
as B cells activate through the body, what must happen in order for them to continue to survive? when does this happen?
B cells must receive signals through BAFF receptors to stay alive; BAFF is encountered when B cells enter secondary lymphoid tissues
what must first happen before B cells can recognize an antigen and begin activation? where does this occur?
in the secondary lymphoid tissues, B cells encounter antigen in follicles, where the BCR binds the antigen
when BCR antigen recognition occurs, is this T dependent or T independent activation?
T dependent
describe T independent activation of B cells (3)
- antigen binds to PRR on B cell
- antigen cross-links with BCR
- this stimulates proliferation of B cell
describe BCR antigen recognition (which is the first step of T dependent B cell activation)
- free antigen binds to BCR
- complement bound to antigen allow for BCR to recognize antigen; occurs as complement protein binds to complement receptor and BCR cross-links to bind to antigen-bound compliment protein
- antigen can bind to subcapsular sinus macrophages (SCSM) or follicular dendritic cells (FDCs) and the BCR will bind to the antigen on these cells
what happens once BCR binds to antigen? (the second step of T dependent B cell activation)
the cell membrane spreads out and then contracts back, leaving microclusters of BCRs along the cell membrane to increase contact with antigen (rearrange location of BCRs on cell membrane)
what happens after BCR microcluster formation? (the third step of T dependent B cell activation)
the BCR and the antigen will be internalized into the B cell
describe internalization of BCR and antigen in the third step if it is free antigen?
happens readily
describe internalization of BCR and antigen in the thir step if antigen is bound to SCSM of FDCs
actin on B cell membrane must polymerize and push against menbrane of SCSM or FDC to pull antigen off the cell
what happens after internalization of BCR and antigen? (fourth step of T dependent B cell activation)
antigen is processed and presented on MHC II of B cell
what happens after antigen is present on MHC II of B cell? (fifth step of T dependent B cell activation)
once antigen is presented on MHC II, the B cell is directed to the T cell zone of the lymph node or splees
what is the T cell zone?
the site of activation in the lymph node or spleen
oncce in the T cell zone, what 3 signals do helper T cells provide for B cell activation (sixth step of T dependent B cell activation)
- TCR binds antigen/MHC II on B cell and CD4 binds MHCII
- CD40L on T cell binds CD40 on B cell
- cytokines are secreted by T helper cells (IL-4 and IL-21)
look familiar?
what cytokines are released by T helper cells during the sixth step of B cell activation?
IL-4 and IL-21
what does the sixth step of T dependent B cell activation, activation, result in? (2)
- B cell proliferation
2. loss of IgD on B cell (will just express IgM for now)
after recieving activating signals from helper T cells,what happens to B cells? (in the seventh step of T dependent B cell activation)
SOME proliferating B cells migrate to the T-B border in lymph nodes or the spleen and develop into a primary focus
what is the primary focus?
a cluster of proliferating B cells
what happens to the plasma and memory cells that come from the primary focus? (2)
- they are only capable of secreting IgM, which is not always the most effective antibody
- the plasma cells travel to the site of infection and secrete that IgM
what happens to the remaining B cells that did not form a rpimary focus upon entering the T-B border? (the eighth step of T dependent B cell activation) (2 things happen)
- the remaining B cells enter the follicles of lymph nodes or spleen and form germinal centers
- in the follicles, follicular helper T cells provide survival signals to B cells (CD40L on T cell binds CD40 of B cell)
what are the two zones of the follicles in the lymph nodes or spleen and what happens in each? (the ninth step of T dependent B cell activation)
dark zone: B cells proliferate and undergo somatic hypermutation then enter the light zone
light zone: B cells undergo selection
describe the process of selection in the light zone (the tenth step of T dependent B cell activation) generally and then give steps (5 steps)
B cells are tested for how strongly they bind antigen
- free antigen in germinal center will bind BCR
- antigen is endocytosed, processed, and presented on MHC II
- TCR (of folliclar helper T cell) binds antigen/MHC II (CD40L binds CD40)
- B cell receives survival signals and recirculates to dark zone for more proliferation and somatic hypermutation (in a cycle)
- cells that don’t strongly bind antigen don’t receive survival signals from follicular helper T cells and undergo apoptosis
what happens to the B cells that DO strongly bind antigen after selection process in light zone/germinal center? (the eleventh step of T dependent B cell activation)
they will undergo class-switching
describe class-switching, generally
the heavy chain of the BCR switches from mu class to either alpha, gamma, or epsilon
what determines the class that the heavy chain of the BCR switches to?
the cytokines that are present during class-switching
what happens after each round of selection (the technical twelfth step of T dependent B cell activation)
after each round of selection, some B cells differentiate into plasma cells, which leave secondary lymphoid tissues and travel to sites of infection to secrete antibodies
give the 12 steps of T dependent B cell activation, beginning with antigen recognition
- BCR antigen recognition
- rearrangement of the location of BCRs on cell membrane to binds more antigen
- internalization of antigen and BCR into B cell
- presentation of antigen on MHC II of B cell
- B cell directed to T cell zone by chemokines
- Helper T cells send the 3 signals for B cell activation, resulting in B cell proliferation
- some proliferating B cells migrate to T-B border and form primary focus
- other proliferating B cells enter follicle and for germinal centers
- in follicles, proliferation and somatic hypermutation occurs in dark zone and selection occurs in light zone
- selection in light zone (cycling back to dark zone and such) leads to apoptosis of B cells that do not strongly bind antigen and
- B cells that do strongly bind antigen undergo class switching
- after each round of selection, some B cells differentiate into plama cells that leave secondary lymphoid tissues, travel to site of infection, and secrete antibodies
what does somatic hypermutation mean, based ont he definitions of each word in the name?
somatic means occurs outside the germline and hypermutation means rapid changes
where does somatic hypermutation occur?
in the variable regions of both light and heavy chains of BCR
what is AID?
activation-induced cytidine deaminase
how does somatic hypermutation begin?
starts when AID changes cytidine to uridine, creating a mismatch that must be corrected and there are 4 ways to correct it
what are the 4 ways to correct the mismatch created when AID changes cytidine to uridine in somatic hypermutation
- U can be repleaced with another C and this will result in no mutation
- U-G pair can be replaced with A-T pair, and the new base pair will result in a new DNA sequence
- U is removed and replaced with any nucleotide, als yields new DNA sequence
- longer strands of bases can be removed and repaired, also yields new DNA sequence
describe the process of class-switching
- AID makes two double-stranded breaks in the switch region: one break before the mu gene, and another break before the gene it is switching to
- the DNA between the two breaks is excised, or removed
- the variable region is joined with the remaining constant region, creating a new class of antibody
can a B cell express any other type of antibody after undergoing class switching? why or why not?
nope, can’t because the other DNA was removed
what is class-switching dependent on?
cytokine secretion
what do the memory cells created from B cell activation allow for?
allow for an almost immediate response upon secondary exposure to the same pathogen
