B Cell Development

Front 1

Provide a general overview of the maturation process of B cell

Back 1

Precursor B cells derived from lymphoid precursor stem cells in the bone marrow remain in the bone marrow during the maturation process
-During this maturation process the B cell will begin to express membrane -bound immunoglobulin (mIg) and Ig alpha/ Ig beta co-stimulatory molecules

Front 2

What does mIg do?

Back 2

it determines the antigen specificity of the B cell

Front 3

What does mIg along with Ig- alpha / Ig-beta costimulatory molecules make up?

Back 3

The B cell receptor or BCR

Front 4

What happens if the mIg of an immature B cells bind an antigen during the developmental process?

Back 4

While still in the bone marrow, the Ig-alpha and Ig-beta co-stimulatory molecules sends a signal to the inside of the cell causing the cell to die. This process of eliminating self-reactive B cells is known as clonal deletion

Front 5

What happens to B cells that are not deleted?

Back 5

They develop into mature B cells that leave the bone marrow circulate in the blood and migrate to the spleen and lymph nodes

Front 6

What is the mIg component of the BCR of a mature, naive B cell?

Back 6

either IgM or IgD

Front 7

What is the structure of mIg

Back 7

Each molecule consists of 4 polypetide chains: 2 identical heavy chains and 2 identical light chains
-Each of the immunoglobulin H and L chains have one V region and one C region
-Vh and Vl regions combine to form an antigen-binding pocket
-2 antigen binding sites per immunoglobulin molecule

Front 8

How many mIg molecules will a mature B cell have?

Back 8

In its membrane, a mature B cell would have approximately 1.5 x 10^5 mIg molecules in its membrane
-All of the Mig molecules (both IgM and IgD) on a single B cell have the same antigen specificity because the mIg molecules have the same Vh and Vl

Front 9

What will a single B cell bind to?

Back 9

Will bind to one or a few similar epitopes (antenic determininants)
-Different B cells will have different Vh and VL regions in the IgM and IgD molecules (due to gene rearangement) and thus different antigen specificity

Front 10

What are the general characteristics of B cell development?

Back 10

-B cells are produced in the bone marrow
-B cell development is tied to B cell receptor gene rearrangement which produces IgM surface molecule that is screeend for reactivity with water soluble molecules and other molecles if not reactivity it mores on

Front 11

What does B cell development require?

Back 11

It requires the production of a functional mew heavy chain and a functional light chain to form the cell surface IgM B cell receptor on immature B cells

Front 12

What happens if immature B cells that express BCRs for self antigens?

Back 12

First these self-antigens are soluble proteins or cell surface molecules
-They are deleted and this is similar to negative selection in the thymus except there is no positive selection by self-peptide/ MHC complxeses for B cells

Front 13

What do immature B cells expressing BCRS that are not reactive with self-antigens develop into?

Back 13

Mature B cells that express both IgM and IgD on their cell surface

Front 14

Why is there no need for presentation of MHC for antigens for B cells?

Back 14

Because B cell receptors detect things outside the cell that are not presented by MHC

Front 15

Mature B cells leave the _______________ and migrate to the ________________ via the _____________

Back 15

bone marrow
secondary lymphoid organs (spleen and lymph nodes)
blood circulatory system

Front 16

Mature B cells remain in a resting state until _____________

Back 16

they are activated by foreign antigens

Front 17

What are the basis for B cell development?

Back 17

1) B cell development is tied to B cell receptor gene rearrangement
2) Each BCR is generated from the random selection of gene segments
3) Immature B cells that express a functional BCR are screened for self-reactivity - those with high affinity BCRS are clonally deleted
4) B cells that are not deleted develop into mature B cells that leave the bone marrow, circulate in the blood and migrate to the lymph nodes and spleen

Front 18

How many signals does B cell activation need?

Back 18

2 Signals

Front 19

What are the two signals required for B cell activation?

Back 19

Signal 1 = Binding of antigen to the BCR- the signal is relayed to the nucleus by the Igalpha/Igbeta cosignalling molecules

Signal 2 = binding of CD40 on the B cell to CD40L on the T cell

Front 20

How does the Th2 support B cell divsion?

Back 20

The Th2 secretes cytokines that help support B cell division and differentiation into plasma cells (that secrete antibodies) or memory B cells

Front 21

Consider this scene:
An APC phagocytosed, processed and presented the antigen fragments on MHC II. The T helper cell was activated. What now?

Back 21

1) The B cell will bind antigen via its BCR that results in the internationlization of the antigen/BCR complex.
2) The antigen/BCR complex is internalized and processed and peptides derived from the antigen are displayed to Th2 cells on MHC (that was activated by a dendritic cell)
3) Interaction between CD40 on B cells and CD40L on Th2 cells is essential for maximum B cell activation
4) Th2 cell also provides cyotkines IL-4 and IL-5 to B cells to promote cell division and differentiation into plasma cells

Front 22

Why do B cell display peptides on MHC II?

Back 22

In order for the T helper to know which B cell needs help, the B cell must somehow identify itself to the T helper cell
-By presenting the same MHC II/peptide complex that the T helper cell has seen before, it can identify itself to the T helper cell as the one that needs HELP!