2-B Lymphocytes

Question 1

characteristics

Answer 1

-responsible for humoral imm
-devel in bone marrow
-precursor to plasma cells
-membrane anchored IgM and IgD
-one antigenic specificity
-exist without need for exposure to antigens

Question 2

antibody responses

Answer 2

primary = naive B cell activated, low anti production IgM>IgG, low affinity of anti

secondary= repeat exposure activates memory B cells, higher plasma cell levels and long lived plasma cells in marrow, inc IgG, high average affinity

Question 3

maturation

Answer 3

1. stem cell
2. pro B (don’t study)
3. pre B
4. immature B
5. mature B

Question 4

pre-B cells

Answer 4

have heavy chains only aka cytoplasmic mu
and VDJ gene, NO antigen response

@ bone marrow

Question 5

immature B cells

Answer 5

have both heavy and light chains with IgM
gets released into periphery

will respond to antigen by neg selection aka will delete itself to destroy having an autoimmune response

Question 6

mature B cells

Answer 6

have IgM and IgD specific for same antigen
will respond to antigen

Question 7

mature B cell differentiation

Answer 7

after activated and proliferates
1. plasma cell for antibody secretion @ lymphoid organs and marrow
2. isotype switching to IgG
3. affinity maturation
4. memory B cell

Question 8

plasma cells

Answer 8

elongated cell, eccentric nucleus, perinuclear halo abundant cytoplasm

terminally differentiated antibody-prouducing machines

only last a few days but some are very long lived in marrow

Question 9

B/T cell interaction

Answer 9

required for anti production but each cells reponds to diff epitope on given antigen

specific to class II MHC so CD4 T cells

B7 on B - CD28 on T
CD40 on B - CD40L on T

Question 10

B cell antigen presentation

Answer 10

1. protein antigen bound by surface antibody
2. receptor mediated endocytosis
3. process then expressed on class II MHC
4. T cell releases cytokines
5. B cell activated
6. antibody producing plasma cell

nonprotein antigens CANNOT be used so no lipids or nucleic acids

Question 11

B cell antibody outcomes

Answer 11

1. neutralization of microbes/toxins
2. opsonization and phagocytosis of microbes
3. antibody dependent cellular cytotoxicity via NK cells
4. phagocytosis of microbes opsonized with complement fragments
5. inflammation
6. lysis of microbes

4-6 via complement activation

Question 12

TD antigens

Answer 12

thymus dependent

protein antigens are TD bc need T-helper cells
-high affinity antibodies, long lived plasma cells

Question 13

TI Antigens

general

Answer 13

thymus independent

non protein antigens don’t need T-helper cells aka polysaccharides, nucleic acids, lipids,

provide all necessary B cell signals, mainly IgM short lived plasma cells
-no memory cells, isotype switching, or affinity maturation

Question 14

TI-1 antigens

Answer 14

bind non immunoglobulin receptors to promote polyclonal expansion

i.e. LPS acts as B cell mitogen

Question 15

TI-2 Antigens

Answer 15

bind thru B cell surface immunoglobulin aka only activate antigen-specific B cells

i.e. polysaccharide antigens with repeated epitopes

Question 16

transduction

Answer 16

signalling thru Ig-alpha and beta

same as CD3 with T cells

Question 17

Ig structure

Answer 17

2 heavy chains + 2 kappa OR lambda light chains

shared constant regions but differing variable regions

Question 18

Ig Genes

Answer 18

heavy and light chains encoded by gene segments on diff chromos

V region = variable
D region = heavy chain diversity
J region = joining
C region = constant

Question 19

gene segments-variable region

Answer 19

variable region of heavy = VDJ segments for antigen binding

variable region of light = VJ segments for bindign

Question 20

molecular diversity

Answer 20

-pairing heavy and light chains
-combinatorial diversity with diff gene segments rearranged
-junctional diversity of nucleotide add/remove at joints b/t segments via TdT
-somatic mutation aka point mutations in variable regions that have been rearranged

Question 21

gene rearrangment

Answer 21

recombinases loop out, excise DNA, then ligate at random
-DNA irreversibly lost during recombination
-progeny B cells inherit same receptor specificity

recombinases encoded by RAG1 and RAG2 genes so if mutations in those then severe combined immunodeficiency (SCID)

Question 22

gene rearrangement sequence

Answer 22

1. heavy chains random D and J segments brought together and intervening DNA deleted
2. V gene randomlly selected and added to 5’ end of DJ segement = VDJ
3. intro separates VDJ from C region gene Cu and CS so that they remain in primary RNA transcript
4. process of primary RNA so splice out introns, remove CS, add poly A tail
5. mRNA > cytoplasmic u-heavy chain of pre B cells

Question 23

allelic exclusion

Answer 23

since inherit 2 sets of heacy chain genes (1 from mom and dad) then if 1st rearrangment is productive then genes on other chromo won’t be rearranged

if all rearranges are nonproductive then cell death

4 light chains (2 kappa and 2 lambda) so kappa gene rearrange 1st then others not rearrange, if nonprod then kappa 2 tries etc..

Question 24

co-expression of IgM and IgD

Answer 24

antigen naive B lymphs express both M and D bc alternative mRNA splicing encodes IgM and D so both specific for same antigen since use same VDJ regions

Question 25

antibody forms

membrane or secreted

Answer 25

if B cells stimulated by antigen then shift to secretory form
-differential splicing of primary RNA transcript that codes for membrane anchored and secreted forms
-if splice out membrane anchor sequence then secrete form

Question 26

isotype switching

Answer 26

antigen stimulation > B lymph switch to diff isotype either by
1. long primary RNA transcript containing VDJ regions and many/all Ch sequences produced then splice out unneeded Ch regions
2. deletion of intervening Ch regions like DNA to align VDJ region with new Ch gene by using switch regions b/t Ch region segments, delete IgM and IgD Ch’s

isotype will dep on T cell cytokines
will always produce one class of light chain so no switching

Question 27

affinity maturation

Answer 27

secondary immune response > higher affinity than in a primary

inc affinity from somatic mutations in V region genes, selected by virtue of inc ability to bind antigen + be stimulated by follicular helper T cells

memory B cells express higher affinity antigen receptor so requires smaller amount of antigen to induce a secondary, if low or no affinity then die by apoptosis