Lecture 7 BCR Diversity and Development

list the three mechanisms for antibody diversity

somatic recombination

gene conversion

somatic hypermutation

Variable domains are constructed from what gene segments?

V, D, and J

what gene segment is specific to the heavy chain

D-diversity gene segment

somatic recombination nis mediated by what

VDJ recombinase enzyme

VDJ recombinase enzyme is made of what

RAG1, RAG2, and DNA repair enzymes

what are two other methods by which somatic recombination creates diversity

imprecise joining

nucleotide addition

define gene conversion

fragments of V pseudogenes are randomly inserted into the V gene segment during proliferation

where does somatic hypermutation occur

in ileal peyer’s patches or secondary lymphoid tissues

define somatic hypermutation

during B cell division, CDR 1 and 2 are hypervariable and single base pairs are exchanged

how many genetic loci on different chromosomes encode for the heavy chain and light chains

3-L, V, and C

what mechanisms for diversity do all animals use

somatic recombination

what is the main source of diversity in primates and mice

somatic recombination

what is the main source of diversity in chickens

gene conversion

somatic hypermutation is primarily used by

mammals

what signals B cell development

stromal cells signal IL-7 secretion

what occurs during pro-B cell development

rearrangement of the DJ heavy chain

after rearrangement of the DJ chain occurs, what is rearranged next?

VDJ of heavy chain

what is rearranged in the pre-B cell

first the kappa light chain is rearranged, then the lambda only if the kappa chain rearrangement is unsuccessful

list the order of B cell development/B cell precursors

HSC > common lymphoid precursor > pro-B cell > immature B cell > mature B cell

an immature B cell expresses what on its cell surface

IgM

immature B that do not recognize self antigen do what

leave the bone marrow into circulation

what is the fate of immature B cells that do recognize self antigen

receptor editing of light chain till no reaction with self antigens

apoptosis

leave the bone marrow as anergenic cells

define anergenic

inability to become active

what aids in the final maturation of immature B cells to mature B cells

B cell Activating Factor (BAF)

define allelic exclusion

ensures that a single B cell only expresses immunoglobulins with 1 specificity

how is allelic exclusion accomplished

successful rearrangements of the heavy chain of one chromosome shuts down rearrangement of the other chromosome (same process occurs with the light chain)

a mature B cell that survives negative selection expresses what

IgM and IgD

isotype determines what

biological activity

isotype/class is identified by what

the constant domain of the heavy chain

define isotype switching

class switching from M to G, A or E after activation

retains specificity

changes biological activity