Dr. Ryan - B-cells (lectures 3 and 4)

when are B cells activated?

after exposure to antigens usually in lymphoid follicles

what is a plasma cell?

antibody producing cell/memory B cell

what are antibodies?

proteins produced by b lymphocytes in response to specific foreign antigens, immunoglobulin

what is the Fab region of antibody?

antigen binding site that binds only to specific epitope, highly variable

what is the Fc region?

determines class, responsible for effector/immune responses

which parts of antibody is part of the Fab region?

light and heavy chain

what part of the antibody is part of the Fc region?

the heavy chain

what are recombination options for heavy chain?

VDJ

what are recombination options for light chain?

VJ

where and when is antigen binding site diversity generated?

during maturation in the bone marrow

what is the variable region of an antibody?

the Fab region

what is the constant region of an antibody?

the Fc region

what tells B cells to rearrange heavy and light chains?

bone marrow stroma

T/F: B cells only get 1 chance to get a functional heavy and light chain

FALSE

which chain is formed first?

heavy chain

which chain is formed second?

light chain

when do B cells get second chances?

after forming the heavy chain and then after forming the light chain

what happens if there is no BCR on a B cell?

the cell dies

what happens if there is a self-reactive BCR?

given a second chance, rearrangement occurs, then if still self-reactive then cell dies

what happens if BCR reacts to soluble protein/super common self-antigen?

there is no cross-linking of receptors and cell becomes anergic

how many CDRs do antigens have?

6

what does CDR stand for?

complementary determining regions

what is another word for CDRs?

hypervariable regions (HVR)

how are HVRs split between the light and heavy chains?

three for each

T/F: BCRs are just membrane bound antibodies

TRUE

what immunoglobulins/antibodies are found on naive B cells as part of the BCR complex?

IgM and IgD, closely associated with Fc portion of antibody

what does activation of B cells do to antibodies?

antibodies shift from being membrane bound to being secreted antibodies

which chain determines the antibody class names?

the heavy chain

When does class switching occur?

with antigen binding and with adequate co-stimulatory molecules

T/F: once a B cell commits to IgE, IgG, or IgA it can return back to IgD or IgM

FALSE

what determines type of class B cell differentiates to?

cytokine profile that the T helper cell secretes

what forms can antibodies come in?

monomers, dimers, and pentamers

T/F: the J chain in pentameric IgM is part of the VDJ segments

FALSE; IS COMPLETELY SEPARATE

what is a J chain in dimers and pentameters

the chain that joins the antibodies together

where is IgA secreted?

concentration is highest in mucosa, respiratory, GI, urinary, skin, mammary gland, eye

how does IgA dimer get to the luminal side of cell?

by the polymeric immunoglobulin receptor (or secretory component) which is endocytosed and moved

what does secretory component do to IgA once it is secreted into lumen?

protects IgA in GI tract from intestinal proteases

which class of antibody is heaviest?

IgM, pentameric

which antibody class is highest in concentration in the blood?

IgG

which antibody class has the highest half-life?

IgG

which antibody is most associated with extravascular secretions?

IgA

T/F: activation of B cells can occur with or without T cells

TRUE

what is the most common and effective way to activate a B cell?

with a T cell

what MHC do B cells present?

MHC 2

what are teh 2 pathways of B cell activation without T cells?

thymus independent antigen TI-1 and TI-2

what is TI-1?

the thymus/T cell independent B cell activation that is a simultaneous activation of BCR and the co-receptor

what is TI-2?

thymus and T cell independent B cell activation that involves the cross-linking og BCR with proteins/polysaccharides

can class switching and/or increasing of affinity occur in B cell activation without a T cell?

no

what is class switching?

switch the type of antibody plasma cells secrete, can never revert to other Ig types because DNA was removed

what is somatic hypermutation?

random DNA base substitutions are made at CDRs, mutations that lead to tighter binding are selected, increasing the affinity

what is the only antibody that can be produced when a B cell is activated without T cell help?

IgM or IgD, but mainly IgM

what class of antibody initially increases at exposure of antigen?

IgM

what class of antibody will be the longer lasting antibody that increases later after exposure to antigen?

IgG

how do antibodies assist with immune responses?

activating cell-dependent activities, enhancing phagocytosis by acting as an opsonin, binding and inactivating toxins, activating complements, and activating B cells