Antigen Recognition by Lymphocytes

Is the variable region the C or N termini?

N termini

Is the heavy chain constant? What does it determine for an antibody?

Yes it is but it also has one variable region. It determines the function of an antibody

What is the expression of different classes of antibodies dependent on?

Activation and development of the B cell

What is the common structure of an antibody?

1. Has 2 identical heavy chains

2. Has 2 identical light chains

3. Has a hinge region

What is a B cell receptor?

It is just an antibody stuck on the surface of a B cell

What are the six features of a BCR?

1. 2 identical light chains

2. 2 identical heavy chains

3. Heavy and light chains are connected by disulfide bonds

4. Contain a hinge region in the heavy chain

5. BCR can bind two or more antigens

6. On the B cell membrane it contains Iga (CD79a) and IgB (CD79b)

Describe the structure of the 2 identical light chains

1. Can be kappa or lambda

2. Have one variable region

3. One constant region

Describe the structure of the 2 identical heavy chains

1. Can be mu, alpha, delta, gamma, epsilon (MADGE)

2. One variable region

3. 3-4 constant domains

What does a hinge region allow for?

Flexibility for antigen binding

Is Ida and IgB part of the BCR or the complex? What is the function?

Complex and it stabilizes the BCR

Where do B cells develop?

In the bone marrow

What happens in the development stage for a B cell?

The BCR is having its DNA rearranged to create a collection of B cells with different binding targets. Development occurs in the absence of a specific antigen

What do mature B cells need to have to exit the bone marrow?

Functional and trustworthy BCRs

What does trustworthy BCRs mean?

It means that the BCR is not going to mount an autoimmune response. They go through a selection process where if they can bind to self then they are deleted.

What is a naive B cell mature enough to get through?

Differentiation and selection and able to get to the periphery

What happens after the mature B cells exit the bone marrow?

The B cell will use its BCR exclusively to detect pathogens

What are 3 functions that B cells perform once they have found their antigen?

1. Continue to recognize it through their BCRs

2. Secrete antibodies

3. May further rearrange their DNA, and change isotypes (improvement program)

Describe how a B cell can make a better BCR

The B cell is able to reactivate some of its editing programs to try to make it better. It can randomly edit by inserting some nucleotides and cutting some out in the variable region. It is also able to start making a different type of immunoglobulin. Lastly, they can change the affinity to which they bind to that particular pathogen

Did the BCR or antibody come first?

BCR

Do the antibodies secreted by a B cell have the same binding targets as the BCR of the B cells that created them?

Yes

What is the difference between a BCR and an antibody?

Alternative RNA splicing

Are antibodies or BCRs made at higher concentrations?

Antibodies

What does the difference between the membrane bound and secreted forms come down to?

A hydrophobic (membrane bound) or hydrophilic C terminus (secreted). Keep the membrane coding region for a membrane bound BCR and keep the secretion coding region for a secreted antibody

What are the 2 types of B cells?

1. B1

2. B2

What are B1 cells?

They are rudimentary B cells while B2 cells are the ones we are always talking about

What are five differences between B1 and B2 cells?

1. B1 cells arise earlier than B2

2. B1 secret antibodies even before activation but B2 cells do not

3. The affinity for B1 BCRs is lower than that of B2 BCRs

4. B1 cells are distinguishable based on their expression of CD5

5. The BCR structure is fundamentally the same but the variable regions differ

When are B1 B cells first produced? B2?

B1: Fetus and on for your whole life

B2: After birth and on for your whole life

Do B1 cells have few or extensive N-regions in VDJ junctions? B2?

B1: Few

B2: Extensive

Is the V-region repertoire restricted or diverse in B1 cells? B2?

B1: Restricted

B2: Diverse

What is the primary location of B1 cells? B2?

B1: Peritoneal and pleural cavities

B2: Secondary lymphoid organs

What is the mode of renewal for B1? B2?

B1: Self-renewing (can sit in the tissues and just keep replicating)

B2: Replaced from the bone marrow (have to be replaced this way to go through the selection process)

Is spontaneous production of immunoglobulin high or low for B1? B2?

B1: High (no help required from MHC or T cells)

B2: Low

What are the isotypes secreted for B1 cells? B2?

B1: IgM » IgG (almost always IgM)

B2: IgG > IgM (can make IgA and IgE)

Is there requirement for T cell help for B1 cells? B2?

B1: No (don’t need to see peptide and MHC like T cells)

B2: Yes (need T cell help to start secreting immunoglobulins)

Is there high or low somatic hypermutation for B1 cells? B2?

B1: Low to none

B2: High

What is somatic hypermutation?

It is when you have a gene loci and you can pick different parts and synthesize them together to meet the diversity of the pathogen it encounters

Can B1 cells have memory development? B2?

B1: Low to none

B2: High

Did B1 cells probably evolve first?

Yes

What are B1 cells?

They are a subset of B cells that lie in between what a B cell does and what an innate immune cell does. They make antibodies like B cells but they also can bind to common features that a pathogen has like a PRR binding to a PAMP. They are good at innate protection due to this

Can B1 cells bind in the native conformation?

Yes

What regions are B1 cells localized to?

Regions exposed to the outside world such as mucus membrane, lungs, gastrointestinal tract as you want to neutralize the pathogen quickly