Lecture 7: B Cell Development

Question 1

What is the sole function of a plasma cell?

Answer 1

Secrete antibodies

Question 2

what does it mean to have a fully differentiated cell?

Answer 2

Cannot differentiate any further

Question 3

A blood stem cell can differentiate into two cells. What are these?

Answer 3

• Myeloid stem cell
• Lymphoid stem cell

Question 4

A myeloid stem cell can differentiate into three cell types:

Answer 4

• Red blood cells
• Platelets
• Myeloblast

Question 5

A myeloblast can differentiate into granulocytes. What are the three granulocytes?

Answer 5

• Eosinophil
• Neutrophil
• Basophil

Question 6

A lymphoid stem cell can further differentiate into

Answer 6

Lymphoblast

Question 7

A lymphoblast can differentiate into:

Answer 7

• B lymphocyte- Plasma cell
• T lymphocyte
• Natural killer cell

Question 8

Granulocytes (Eosinophil, Neutrophil, Basophil), Plasma cell, T lymphocyte, Natural killer cell are all

Answer 8

White blood cells

Question 9

Stages of B Cell development

Answer 9

1. B cells develop from pluripotent stem cells in the bone marrow.
2. The stem cell develops into a mature IgM+ B cell.
3. The mature, naive B cells circulates through the peripheral lymphoid organs.
4. B cells that fail to encounter antigen die through apoptosis.
5. B cells that encounter antigen (1st signal) and receive a second signal are activated.

Question 10

B Lymphocytes are predicted to generate approximately 1x10^11 distinct antigen receptors.
However, the human genome only contains about 25,000 distinct genes.
How does such a limited genome enable the generation of an almost infinite number of antigen receptors?

Answer 10

Germline organization of a gene

Question 11

Explain the germline organization of a typical gene

Answer 11

1. In a genomic DNA, there is a promoter and various types of exons (ex: exon 1 and exon 2).
2. Transcription happens and it’s gonna result in a primary transcript (has both exons 1 and 2).
3. Splicing results in formation of mRNA
4. Translation combines both exons 1 and 2 and forms a protein.

Question 12

What happens in the diversity by V(D) J Somatic Recombination?

Answer 12

1. V, D, and J gene segments are in tandem.
2. In a single lymphocyte clone, one D gene segment randomly recombines with one J gene segment.
3. A V gene segment then recombines with the D-J segment, generating a recombined V-D-J gene.
4. The new gene is then transcribed. The V-D-J gene segment is spliced to the first C region (μ Chain).
5. The resulting mRNA is translated to generate a unique IgM heavy chain.

Question 13

The germline organization of antigen receptor gene loci

Answer 13

• The Ig heavy chain locus contains variable (C) region gene segments.
• The variable region gene segments are followed by diversity (D) and joining (J) gene segments.
• VDJ segments are followed by sequentially arranged constant gene segments.
• The light chain loci displays a similar organization to the heavy chain locus, except it lacks any D gene segments. There are two light chain loci - κ and λ

Question 14

Each gene recombination generates a unique ______ region. - unique antigen specificity.

Answer 14

variable

Question 15

The _______ region, does not change- conserved effector function.

Answer 15

constant

Question 16

What are sources of diversity?

Answer 16

• number of V gene segments.
• number of diversity (D) gene segments.
• number of joining (J) gene segments.

Question 17

Stages of B cell activation
(starts with Naive B cell encounters antigen)

Answer 17

1. Naive B cell encounters antigen.
2. Helper T cells stimulate B cells.
3. Activated B cells begin clonal expansion.
4. Some B cells differentiate into antibody secreting plasma cells.
5. Others (some daughter cells) become memory cells.
6. Others switch class to produce a new Ig isotype.

Question 18

Memory Lymphocytes

Answer 18

• produced from naive lymphocytes as a result of antigen exposure.
• persist for years in an inactive state. Rapidly reactivated by repeat exposure to antigen and mediate faster, more potent immune responses.
• some active lymphocytes differentiate into memory lymphocytes.

Question 19

Secondary vs. Primary Antibody Responses

Answer 19

• Secondary responses are more effective at dealing with infections.

Primary response:
Lag after immunization: usually 5-10 days
Peak response: smaller
Antibody isotype: usually IgM>IgG
Antibody affinity: lower average affinity, more variable.

Secondary response:
Lag after immunization: usually 1-3 days
Peak response: larger
Antibody isotype: Relative increase in IgG and, under certain situations, in IgA or IgE (heavy chain class switching)
Antibody affinity: higher average affinity (affinity maturation)

Question 20

Class Switching

Answer 20

changing of an antibodies constant region.

A clone of B cells is not committed to make a single Ig isotype forever.

Does not affect the variable region.

1. Cytokine induce rearrangements at the heavy chain locus.
2. Exposed DNA ends are joined together.
3. End result: New class of Ig (ex: IgG)
4. DNA encoding some constant regions is deleted.

Question 21

Role of cytokine signals in class switching

Answer 21

induce rearrangements at the heavy chain locus.

Question 22

In class switching, the antibody retains antigen specificity. However,

Answer 22

new constant region = new effector functions.