Bioms: B Lymphocytes

Front 1

Where do B cells come from?

Back 1

verbal response

Front 2

What happens to B cells in the bone marrow?

Back 2

verbal response

Front 3

How is B cell differentiation linked with Ig gene rearrangement?

Back 3

verbal response

Front 4

What are the B cell developmental "checkpoints" that ensure each cell produces a single specificity of antibody that does not react with self?

Back 4

verbal response

Front 5

lymphocyte development

Back 5

1. occurs in primary lymphoid tissues
2. ex: bone marrow, fetal liver, thymus, sometimes CALT
3. lymphocytes are sequestered from foreign antigens during development
4. most important event: generation of antigen receptor

Front 6

Secondary Lymphoid tissues

Back 6

1. site of antigen activation
2. ex: lymph nodes, spleen, MALT
3. structured to promote interactions among antigen, APCs, T lymphocytes, and B lymphocites

Front 7

bone marrow derived cells

Back 7

1. hematopoetic cells
2. lymphocyte progenitor cells

Front 8

lymphocyte progenitor cells

Back 8

1. come from bone marrow
2. can develop into B lymphocytes in bone marrow, fetal liver
3. can migrate to thymus to develop into T lymphocytes

Front 9

B lymphocyte receptor

Back 9

1. antibody
2. binds to antigens in native conformation
3. receptor generation mechanism similar to T lymphocyte receptor

Front 10

T lymphocyte receptor

Back 10

1. TCR
2. binds to peptides after processing by APC
verbal response
3. receptor generation mechanism similar to B lymphocyte receptor

Front 11

Severe combined immunodeficiency (SCID):

Back 11

1. immune deficiency where neither antibody or T-cell responses are maid
2. result of genetic defect
3. fatal in childhood if not treated

Front 12

common features of receptor generation in T and B lymphocytes

Back 12

1. DNA rearrangement and repair
2. similar sequence of gene rearrangements
3. surrogate proteins employed in selection
4. positive and negative selection of receptors
4. allelic exclusion

Front 13

B lymphocyte development migration

Back 13

1. lymphocyte progenitor cell develops in bone marrow and leaves primary tissue as "immature B lymphocyte"
2. enter secondary tissue and compete for space to become "mature B lymphocytes"

Front 14

B cell development (6 phases)

Back 14

Phase 1: repertoire assembly
Phase 2: negative selection
Phase 3: positive selection
Phase 4: searching for infection
Phase 5: finding infection
Phase 6: attacking infection

Front 15

B cell development: Repertoire assembly

Back 15

1. Phase 1
2. generation of diverse and clonally expressed B-cell receptors in bone marrow

Front 16

B cell development: negative selection

Back 16

1. Phase 2
2. alteration, elimination, inactivation of B-cell receptors that bind to components of human body

Front 17

B cell development: positive selection

Back 17

1. Phase 3
2. promotion of fraction of immature B cells to become mature B cells in secondary LT

Front 18

B cell development: searching for infection

Back 18

1. Phase 4
2. recirculation of mature B cells between lymph, blood, and secondary LT

Front 19

B cell development: finding infection

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1. Phase 5
2. activation and clonal expansion of B cells by pathogenic antigens in secondary LT

Front 20

B cell development: attacking infection

Back 20

1. Phase 6
2. differentiation into antibody-secreting plasma cells and memory B cells in secondary LT

Front 21

What is the sole purpose of B cell?

Back 21

to make an immunoglobulin

Front 22

pro-b cells

Back 22

1. earliest identifiable cells of B cell lineage
2. main event: rearrangement of heavy-chain genes

Front 23

pre-b cells

Back 23

1. B cell expressing a u chain
2. large: rearranged heavy chain gene; H chain rearrangement stops; cell replicates; produces many daughter cells with identical H chains
3. small: light chain rearrangement; kappa followed by lambda if unsuccessful; when successful light chain assembles with heavy chain in ER; BCR transported to surface
*can attempt more than on VJ rearrangement at a light chain locus --> occurs at light chain loci rather than heavy)

Front 24

B cell development lineage

Back 24

1. hematopoietic stem cell
2. lymphoid progenitor cell (partial heavy chain gene rearrangement)
3. pro-B cell (complete heavy chain gene rearrangement; VDJ expressed)
4. pre-B cell (light-chain rearrangement)
5. immature B cell (change in RNA processing; makes IgM)
6. mature B cell (makes IgM and IgD)

Front 25

allelic exclusion

Back 25

1. alternate allele is not expressed
2. display of one gene product on the cell surface inhibits rearrangement of the second allele

Front 26

pre b cell receptor

Back 26

1. resembles a BCR
2. surrogate light chain checks H chain for quality
3. does not need to be transported to surface in order to provide survival signal

Front 27

Checkpoints

Back 27

1. surrogate light chain provides first checkpoint in B cell development
2. light chain provides second check point
3. cell apoptoses if pre-BCR cannot assemble
4. cell is deleted if BCR binds to a self-antigen

Front 28

What happens in the absence of allelic exclusion?

Back 28

1. structurally substandard BCR
2. low-avidity binding
3. provides weak signal to cell

Front 29

avidity

Back 29

strength of binding betwen >1 receptor/ligand pair (multiple binding sites)

Front 30

self-reactive B cells

Back 30

1. retained in bone marrow
2. receptor editing occurs in immature B cells

Front 31

receptor editing

Back 31

1. occurs when immature B cells display self-reactive igM
2. cell replaces rearranged V(L) domain by new V(L) domain (creates IgM with different specificity - if not keeps rearranging until out of possibilities, then apoptosis occurs)
3. ensures successful H chain rearrangement are not lost

Front 32

soluble self-antigen

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1. cause cell to become anergic (unresponsive)
2. contributes to central and peripheral tolerance to "self"

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Mature Naive B cell

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when B cell escapes "self-antigen" perils

Front 34

central tolerance

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tolerance to self antigens that is generate in B cell populations during their development in the primary lymphoid organs

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peripheral tolerance

Back 35

tolerance to self antigens that is acquired by the lymphocyte population outside the primary lymphoid organs