2.3.8 B-cell development Flashcards by Adriana Beruvides

what is the major antibody secreting cell?

plasma cell

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order of negative and positive selection in T cells and B cells

T-cells: Positive selection first, then negative
B-cell: Negative selection first, then positive

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B cells develop in the ____ then go to the ______

BM, secondary lymphoid organs

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T cells are derived from _____ in the ____, then go to the ______, then to the ______

stem cells
BM
thymus
secondary organs

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both B and T cells are derived from the ______

hematopoeitc stem cell

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what does a hematopoietic stem cell express that is a marker of immaturity?

CD34

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what is a specific B cell marker that is only seen on B-cell precursors?

CD19

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what is the specific marker for T cells?

CD3

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what are the steps of b-cell maturation?

heavy chain rearranged (u)
light chain rearranged (kappa or lambda)
wont see expression of IgMk or IgMl until immature B cell stage

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_________ provides the IL7 signal

stromal cell

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bone marrow stromal cells play an important role in what?

B-cell maturation

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_____ is a critical cytokine in the development of B-cells

IL7

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______ is critical for the development of T cells

Notch 1

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Developing early B cells have a ______ receptor that allow it to bind IL7 cytokines and turn into an immature B cell

IL7 receptor

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steps of rearrangement on B-cells

heavy chains rearrange (if no rearrangement, go through apoptosis- 50% cells)
light chains rearrange on first chromosome (if no rearrangement, move to second chromosome)
light chains rearrange on second chromosome (if unsuccessful, apoptosis- 50%)
productive light and heavy chain = pre-B cell

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Pre-B receptors have a _____ light chain and when light chain rearrangement takes place a functional B-cell receptor is expressed.
What are also parts of the B cell receptor that sends signals to the cell interior?

Surrogate
IgB and IgA

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can successful rearrangement happen on both the maternal and paternal chromosome heavy chains?

no! can only be on one, when a successful rearrangement happens, the other chromosome is shut down

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During light chain rearrangement, _____ is first, and if that is unsuccessful then _____ is rearranged. if both are unsuccessful, apoptosis happens

Kappa (on first then second chromosome)
Lambda (on first then second chromosome)

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what is the ratio of kappa: lambda light chains?

2:1

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how many checkpoints are there in B-cell development?

2: heavy chain and light chain checkpoints

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what are the functions of the following proteins?
1. IL-7 receptor
2. Ig-alpha, Ig-Beta
3. CD-19

growth factor receptor
signaling protein
signal transduction, specific marker for B-cells too

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what are the differences between the B1 and B2 lineages?

B1:
- first B-cells produced in bone marrow before birth
-can self replicate
-result in: short lived plasma cell

B2:
- start production after birth
- result in: short AND long lived plasma cells

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do B1 cells disapear after birth?

where can you find short-lived plasma cells?

medullary cords or red pulp of spleen

the isotypes secreted from B1 cells are ______ and for B2 cells the isotypes are ______

B1: IgM B2: IgG > IgM

do B1 cells require T cell help? what about B2?

B1 cells do not require T cell help, but B2 cells do

if an immature B cell does not recognize self, what happens?

goes out in blood and acquires IgD

if an immature B cell does recognize self, what happens?

it is retained in BM, goes through self-editing in light chain to try to become non-self reactive. -if it does produce a non-self reactive B cell it can leave BM -if it does NOT produce a non-self reactive B cell, it goes through apoptosis

what happens if IgM on surface of self-reacting B-cells reacts with a soluble univalent self antigen?

it becomes anergic

what is peripheral tolerance? what happens?

when self antigen develops outside of BM, B-cells either die or become anergic

how does a B-cell move through a lymph node?

enters HEV --> primary lymph node follicle --> become mature naive B cell --> leave by efferent

explain the interaction of B-cells with FDCs and chemokines! What kind of selection is this?

B-cells come into HEV --> chemokines attract B-cells to primary follicle --> interact with FDC --> drives maturation of immature B-cells --> mature B-cells leave lypmh node - positive selection

Is the FDC derived from the hematopoietic stem cell? Does it belong to the dendritic family?

no and NO!

why is FDC called a dendritic cell?

it displays dendritic extensions where b-cells can interact for signals of maturation (if B-cells dont interact with FDC, they become apoptotic)

B-cell leaves the bone marrow as a ______ with which chains rearranged?

immature B-cell Both light and heavy

where are plasma cells found in the lymph node?

medullary cords

are plasma cells usually found in the blood circulation?

NO this means something is wrong!

________ make antibodies for micro-organisms outside cells, and _____ deal with micro-organisms inside the cells

B-cells T-cells

what are 3 things antibodies can do?

1.neutralization 2. opsonization 3. complement activation

when do B cells become activated?

when their receptors are cross-linked by antigens

Activation signal is transmitted to cytoplasm by ______

Ig-alpha and Ig-Beta

______ is part of the co-receptor and is a specific marker for B cells. what are the other parts of the co-receptor?

CD19 -CD21 (CR2), CD81

what are the T-cell co-receptors?

CD28, B7

T cells express ______ and dendritic cells express ____

Cd28 B7

what are the 2 responses B cells can have to antigens?

T-dependent and T-independent

T-dependent responses all involve the _____ lineage and T-independent responses all involve the ____ lineage

B2 B1

The T-cell subset involved in T-dependent antibody responses are called the ____ subset. This has recently been split up into what?

TH2 TH2/TfH

what is the difference between TH2 and TfH subsets?

TH2 leaves lymph node as an effector cell TfH cell goes to B-cells region of lymph node

TH2-TfH responses are associated with _______ (4) and inhibited by _______(2)

- IL4, IL6, IL10, IL13 - IL12, Gamma-IF

IL12 is made by ________

macrophages or dendritic cells

T-dependent responses by B-cells involve _______ T-cells of the TfH subset

CD4+

are T-dependent or T-independent used for the majority of responses?

T-dependent

basic steps of T-dependent activation

1. B cell associates with antigen 2. MHCII recognized by Helper T 3. T-cell releases cytokines and drives B cell to differentiate into plasma cell

what are the 2 different signals involved in activation process?

1. First signal: B-cell interacting with its specific antigen through B-cell receptor 2. Second signal: interactions of TCR with MHCII on surface of B cell that has the processed antigen **CD40 on B cell must interact with ligand CD40-L on T-cell**

when is antibody produced?

after B-cell differentiates into plasma cell