By lymphocyte development and antibody production

Question 1

Stages of B cell development (antigen independent steps)

Answer 1

1. stem cell committed to the B cell lineage
2. pro B cell (heavy chain rearranges)
3. pre B cell ( heavy chain transcribed/translated and in cytoplasm) light chain rearranges
4. immature B cell - IgM expressed at cell surface, tolerance occurs
5. mature Naive B cell- both IgM and IgD on cell surface

Question 2

B cell development (antigen dependent)

Answer 2

1. activated B cell -> clonal proliferation

2. B cell differentiation with T cell help ( isotype swithching, somatic hypermutation, memory)

Question 3

pro-B cells

Answer 3

first cells derived from hematopoietic stem cells committed to the B lymphocyte lineage
heavy chain gene rearrangement occurs in pro-b cells. successful VDJ-C rearrangement -> expression. ends with formation of functional heavy chain

Question 4

pre-B cells

Answer 4

presence of “mu” heavy chain. two heavy chains combine with two surrogate light chains. (lambda 5 and VpreB). forms the pre-B cell heavy chain. halts heavy chain gene rearrangement and drives multiple rounds of cell division prior to the start of light chain gene rearrangement. ends with functional light chain. (kappa or lambda)

Question 5

immature B cells

Answer 5

IgM bearing B cells. they do not proliferate or differentiate in response to antigen. any encounter with antigen at this stage results in tolerance rather than activation. B cells migrates out of the bone marrow and into the peripheral circulation where it continues to mature

Question 6

mature Naive B cell

Answer 6

immature B cells enter secondary lymphoid organs. express IgD on their surface and become a mature B cell. Naive B cells express BCRs of the IgM and IgD isotypes. The IgM and IgD molecules expressed on the same cell have the same V region and therefore the same antigenic specificity.

Question 7

activated B cells

Answer 7

B cells that encounter antigen, stimulated by antigen-mediated BCR crosslinking.

Question 8

plasma cells

Answer 8

plasma cells produce an enormous quantity of secreted Ig and little membrane Ig and have a distinct morphology.

Question 9

memory cells

Answer 9

long lived and remain in circulation waiting for the next encounter with the same antigen.

Question 10

secondary antibody response

Answer 10

memory cells generate secondary antibody response by differentiating into plasma cells after a second encounter with antigen.

Question 11

checkpoints

Answer 11

imposed to assure B cells receptor formation and function

• every step is checked to make sure that the lymphocyte is still fuction
• if a cell fails to rearrange one of its heavy chains, it will attempt to rearrange the other copy
• both alleles at the k-locus will attempt to rearrange before changes occur at the lambda-locus

Question 12

consequence of check points

Answer 12

2/3 will express the kappa light chain and 1/3 will express the lambda light chain

Question 13

clinical use of checkpoints

Answer 13

evaluation of lymph node or lymphadopathy

Question 14

check point: inflammatory process

Answer 14

ration will remain 2/3

Question 15

check point: B cell malignancy

Answer 15

ratio will be skewed due to the clonality of the transformed cells.

Question 16

autoreactivity is a risk because

Answer 16

V(D)J was random and antigen-independent

Question 17

tolerance promotes

Answer 17

nonreactivity of immune cells to self-tissues and prevents autoimmunity

Question 18

process of tolerance

Answer 18

1. BCR engagement of an immature B cell IgM+ IgD- results in the loss of the cell via clonal deletion or anergy
2. immature B that do not recognize antigen mature as they move through the 2ndary lymphoid organs and become mature B
3. BCR engagement of a mature B cell-> activation, proliferation and antibody production

Question 19

colonal deletion

Answer 19

programmed cell death

Question 20

anergy

Answer 20

functionally inactivated

Question 21

assumptions of tolerance

Answer 21

1. self molecules are constantly present and induce tolerance during development
2. non-self components are transiently present; therefore, mature cells react to eliminate them when they appear. Immature B cells are likely to be tolerized

Question 22

The clonal selection paradigm

Answer 22

1. establish and maintain diverse antigen-reactive B cell clones that is devoid of pathogenic autoreactivity
2. selectively activate, expand, and modify these clones based on antigenic experience