5. B Lymphocytes Flashcards by Georgia Leggett

3 core protective roles of antibodies

Neutralisation
Opsonisation
Complement activation

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What are leukocytes?

All white blood cells

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What are lymphocytes?

B cells

T cells

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Adaptive immunity

Improves efficacy of innate immune response
Highly targeted- Focuses a response on site of infection and organism responsible
Has memory
Needs time to develop

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Antigen

Protein/ molecule that is recognised by immune system

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Epitope

Region of an antigen which receptor binds to

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What is the difference between the types of epitopes recognised by B cells and T cells?

T cells = linear epitopes e.g. AA sequences

B cells = structural epitopes e.g. tertiary structure

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Which lymphocytes are involved in humoral adaptive immunity and how?

B Cells

Antibodies

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Which lymphocytes are involved in cell mediated adaptive immunity and how?

T cells

Cytokines, killing

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Describe B cell generation and maturation

Occurs in bone marrow in absence of antigen
Derived from haematopoietic stem cells
Start as progenitor B cell
Migrate into circulation and lymphoid tissue
Mature B cells are specific for a particular antigen

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Where does specificity for an antigen reside in B cells?

B cell receptor (BCR)

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Describe clonal selection

Each lymphocyte bears a single, unique receptor
Interaction between a foreign molecule and that receptor leads to activation
Differentiated effector cells of that lineage will bear the same receptor

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When are self specific receptors deleted?

Early in development

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Where are B cell receptors found?

Present in 1000s of identical copies on surface of B lymphocyte

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Describe the structure of the BCR

Transmembrane protein complex composed of Ig Mu and di-sulfate linked heterodimers, Ig alpha and Ig beta.
Ig alpha and Ig beta heterodimers contain immunoglobulin-fold structure
The cytoplasmic tail of Ig Mu is too short to signal
The cytoplasmic tails of Ig alpha and Ig beta are long enough to interact with intracellular signalling molecules
Contain ITAM domains

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How does the structure of the BCR transmit its signal into the cell?

Antigen binding to the BCR causes a conformational change, which drives signaling via the Ig-alpha Ig-beta heterodimer

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What is the problem with antigen diversity?

Exposed to incredibly large variety of antigenic determinants
Can’t predict which will be encountered, so immune system must be able to respond to all
But - adaptive immune system is exquisitely specific
∴ need a huge pool of cells with specific receptors that can recognise huge array of antigens

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How does the body deal with antigen diversity?

Encode a massive repertoire
10^10 different antibodies can be generated
Each is produced by a B lymphocyte expressing a specific BCR
25,000 genes for all functions

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How is antigen receptor diversity generated?

Recombination
Each BCR receptor chain (kappa, lambda and heavy chain genes) is encoded by separate multigene families on different chromosomes
During B cell maturation these gene segments are rearranged and brought together
= Immunoglobulin gene rearrangement

Describe the generation of variation in the light chain.

There are 30-40 different V and 4-5 J regions
B cell begins with germline DNA and cuts out V and J regions at random leaving only a few
Different splicing patterns give rise to more variation
VD(J) recombinase loops DNA together & chops out unwanted bit

What is VD(J) recombinase?

An enzyme complex containing the proteins Rag1 and Rag2

Removes unwanted DNA

What does deficiency of Rag genes result in?

SCID

As unable to do recombination

How is generation of variation in the heavy chain different to that in the light chain?

Recombination of V, D and J
Constant regions functional
Constant region achieved by alternate splicing

2 types of light chain

Kappa

Lambda

What determines the class of the immunoglobulin?

Constant region of the heavy chain

In what order does the gene rearrangement take place?

heavy chain undergoes rearrangement before the light chain

Naïve B cell

Antigen specific cell that has never met its antigen

What are the 3 key B cell pathways after antigen exposure?

Become plasma cells involved in antibody production Affinity Maturation Memory

What is the general rule about B cell and T cell activation?

Need co-stimulation from an accessory signal to be activated antigen alone is not enough

Examples of accessory signals for naive B cells

Directly from microbial constituents | From a T helper cell

What are the 2 pathways by which B cell production is achieved?

``` Thymus dependent (T helper cell, all Ig classes, memory) Thymus independent (microbial constituents, only IgM, no memory) ```

Describe the T independent pathway.

often bacterial polysaccharide with a repeating subunit Repeating unit can bind to several BCRs and drive cross-linking 2nd signal provided by microbial constituent PAMPs such as LPS provide co-stimulation

Describe the T dependent pathway.

Dendritic cells and B cells recognise, internalise and degrade antigen B cells present the antigen on MHC Class II Dendritic cells also present the SAME antigen on MHC Class II to a T helper cell The T helper cell becomes activated and undergoes clonal selection The T helper cell then moves to the lymph nodes, comes into contact with the B cell and activates it

T-B Cell collaboration

Activated B cells express lympho(cyto)kine receptors T cell derived cytokines bind to receptors on B cells B cells proliferate and differentiate into antibody secreting plasma cells or memory cells

Describe the process of immunoglobulin class switching.

``` T helper cells (once bound to the B cell) can release various cytokines depending on the cytokine released, Ig class can be switched ```

What does IL-2 allow B cells to do?

Proliferate

What changes in an Ig class switch?

VDJ region stays the same | Cytokines lead to different exons being translated for different constant region

What are the 3 types of B cell?

Naïve: No previous exposure Effector: Plasma cell, secrete antibodies Memory: Longer life span

What drives the improvement of the immune response between primary and secondary exposures?

Somatic Hypermutation and Affinity Maturation

Describe the process of somatic hypermutation.

Point mutations are induced in the VDJ regions by AID which cause slight conformational changes in the antigen-binding site. If the change is beneficial and improves the binding between antibody and antigen then it survives Otherwise the B cells are killed by apoptosis

What is AID in somatic hypermutation?

Activation-induced deaminase enzyme Induces point mutation in VDJ region Swaps C to U, GC pairs become AT pairs

Immunological memory

consequence of clonal selection Antigen-specific lymphocytes (B + T) are the cellular basis More rapid and heightened immune reaction that serves to eliminate pathogens fast Can confer life-long immunity to many infections

What is immunological memory the basis of?

Vaccines

B cell usage

Major vaccine targets as induce antibody response | Monoclonal antibodies are exploited for cancer, asthma, pregnancy testing

When do B cells become a problem?

Autoimmune conditions e.g. Myasthenia gravis Allergy – IgE in anaphylaxis Can tip into cancers (lymphomas and myelomas) especially under influence of viruses e.g. EBV

Why is secondary response better?

Antibody quality improves over time (affinity maturation) | Response is rapid and heightened