Handout 12 part 2: B cell Activation and Antibody Production Flashcards
How is B cell activated initiated?
by specific recognition of Ags by BCRs
How is B cell proliferation and differentiation stimulated?
Ags and other stimuli stimulate proliferation and differentiation of specific B cell clone
What are the various types of cells that B cells can differentiate into after they have proliferated?
Can differentiate into plasma cells that produce IgM other Ig istoype may undergo affinity maturation persist as memory cells
Summary of humoral immune response (how B cells proliferate and differentiate)
Ag recognition by Naive IgM+, IgD+ B cell
Activation of B cell by Helper T cells and other stimuli
Proliferation:
Plasma cell (IgM)–>Ab secretion
IgG expressing B cell–>isotype switching
High affinity Ig expressing B cell–>Affinity maturation OR Memory B cell
What is the result of alternative processing of a primary RNA transcript?
formation of mRNA for the membrane OR secreted form of the mu heavy chain
What does B cell differentiation result in?
results in increasing fraction of the mu protein produced as the secreted form
What parts of the IgM do the following terms refer to:
TP
TM
CY
TP=tail piece
TM=transmembrane
CY=cytoplasmic segments
What are Cmu1, Cmu2,Cmu3, and Cmu4?
They are four exons of the Cmu gene
Define the following acronyms: CDR Fab Fc VH VL CH/L
CDR=complementarity-determining region Fab=antigen binding fragment Fc=crystallizable fragment VH=variable domain of heavy chains VL= variable domain of light chains CH/L=constant domain of heavy/light chains
Where is the CDR found in the Ig? Where does the Ag bind? Which region is associated with effector functions? Which end of the Ig has the amino end and which has the carboxyl end?
CDR found in variable regions of heavy and light chains
Ag binds to Fab region of Ig
Fc portion is associated with effector functions
Fab (Ag binding region) has amino end, and Fc fortion of heavy chain has carboxyl end
To which domain does C1q bind? Which domains are found in all Igs? Which domains are specific to only a few Igs? What are these Igs?
C1q binds to CH2 domain
CH1, CH2 and CH3 are found in all Igs but CH4 is ONLY found in IgE and IgM!
In what kind of immune response (T-dependent or T-independent?) do B cells undergo heavy chain isotype class switching? What are the Igs that undergo class switching and what kind of heavy chains do these Abs produce?
Activated B cells that express IgM and IgD in T-cell DEPENDENT responses undergo heavy chain isotype (class) switching
They produce Abs with heavy chains of classes like gamma, alpha and epsilon
Where does isotype switching primarily occur? What kind of cells drives this process?
isotype switching mainly occurs in germinal centers and are driven by follicular T helper cells
some isotype switching may also occur in B cells in extrafollicular foci, driven by extrafollicular Th cells
What is the advantage of being able to switch Ab isotypes?
B cells producing different Ab isotypes provides plasticity in humoral immune responses
Abs of different classes perform different effector functions and are involved in defense against different types of pathogens
Which part of the Ig is involved in class-switching?
Class-switching occurs in response to changing the constant regions of the heavy chains
How is specificity of class-switched Abs maintained?
Specificity is determined by the variable regions which remains unaltered during class-switching
B cells activated what kind of signals undergo Ig isotype switching?
B cells activated by Th cell signals–CD40L, cytokines
Each class of Abs mediates distinct effector functions. What are the principal effector functions of each of the following classes of Abs: IgM IgG (subclasses: IgG1, IgG3) IgE, IgG4 IgA
IgM: Complement activation
IgG subclasses (IgG1, IgG3): Opsonization and phagocytosis; complement activation; neonatal immunity (placental transfer)
IgA: Mucosal immunity (transport of IgA through epithelia)
What cytokine is needed to convert an activated B cell into each of the following classes of Abs:
IgG subclasses (IgG1, IgG3)
IgE and IgG4
IgA
IFN-gamma needed to switch into IgG subclasses (IgG1, IgG3)
IL-4 needed to switch into IgE and IgG4
TGF-beta, APRIL, BAFF in mucosal tissues needed to switch into IgA
How is isotype switching regulated in response to different types of microbes?
Regulated by cytokines produced by Th cells that are activated by microbes
IFN-gamma induces B cell switching to ___ and IL-4 induces switching to ___
IgG (Th1)
IgE (Th2)
What is the function of IgG Abs?
They respond to viruses and intracellular bacteria and involves IgG Abs which block entry of microbes into host cells and promote phagocytosis by macrophages
Intracellular pathogens activate which subset of helper T cells? What cytokine does this subset of T cells produce?
Activate Th1 cells which produce IFN-gamma and also induce IFN-gamma follicular T helper cells to make more IFN-gamma
What is the major function of IgE?
Response to helminths
Participates in eosinophil and mast cell-mediated elimination of the helminths