B cells: Development, activation and humoral immunity

Question 1

Development of B cells

Answer 1

occurs in the bone marrow
antigen independent

Question 2

In lymphoid organs (spleen, lymph nodes)

Answer 2

Activation, affinity maturation and differentiation to plasma and memory B cells occur
Antigen dependent

Question 3

Primary mechanism:

Answer 3

V(D)J recombination

Question 4

Secondary mechanisms:

Answer 4

Somatic hypermutation Class switch recombination

Question 5

(HSC)

Answer 5

multipotent hematopoietic stem cell

Question 6

Receptor editing:

Answer 6

Non-productive light-chain gene rearrangements can be
rescued by further rearrangement

Question 7

If all rearrangements of κ-chain genes fail to yield a productive light-chain join

Answer 7

λ-chain gene rearrangement may succeed (not shown).

Question 8

V(D)J recombination involves specific DNA sequences and lymphocyte-
specific and ubiquitously expressed DNA repair factors

Answer 8

1. Recombination is directed by signal sequences (RSS)
2. Segments are joined and cleaved by the lymphocyte specific RAG1/2 (Recombination Activating Gene) complex
3. Ends are joined by ubiquitously expressed DNA repair proteins (NHEJ)

Question 9

Describe the phenotypic and functional differences between T1 and T2 immature B cells.

Answer 9

T2 cells have intermediate levels of IgD, whereas T1 cells have no to low amounts of IgD. T2 cells bear both CD21 and CD23, whereas neither antigen is expressed on T1 cells. T2 cells have higher levels of the receptor for the B-cell survival factor BAFF than do T1 cells. Interaction of antigen with T1 cells results in apoptosis; interaction of antigen with T2 cells sends survival and maturation signals.

Question 10

Following expression of the pre-B-cell receptor on the progenitor B-cell surface, the B cell undergoes a few rounds of cell division. What purpose do these rounds of cell division serve in the development of the B-cell repertoire?

Answer 10

Cell division at this stage allows the repertoire to maximize its use of B cells in which a heavy chain has been productively rearranged. Each daughter cell can then rearrange a different set of light-chain gene segments, giving rise to multiple B-cell clones bearing the same heavy chain, but different light-chain genes.

Question 11

Immature B cells bearing potentially autoimmune receptors can be managed in three ways to minimize the probability of disease. Describe these three strategies, noting whether they are shared by T-cell progenitors.

Answer 11

(1) They can undergo apoptosis, in a process called negative selection. This occurs for B cells in the bone marrow and for T cells in the thymus.
(2) They can become anergic—refractory to further stimulation—and eventually die. This occurs for both T and B cells.
(3) Their receptors can undergo receptor editing. This occurs quite frequently in B cells. In T cells, the extent to which receptor editing occurs varies according to the nature of the animal (the nature of the transgene used to study editing), and therefore whether it is a meaningful mechanism in T-cell receptor development and selection is so far unclear.

Question 12

Name one distinguishing feature of TI-1 and TI-2 antigens.

Answer 12

• TI-1 antigens are mitogenic and induce activation through both the BCR and innate immune receptors.
• TI-2 antigens bind tightly to the complement components C3d and C3dg, and so are bound by both the BCR and the complement receptor CD21 (CR2).