2-B Lymphocytes Flashcards
characteristics
-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
antibody responses
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
maturation
- stem cell
- pro B (don’t study)
- pre B
- immature B
- mature B
pre-B cells
have heavy chains only aka cytoplasmic mu
and VDJ gene, NO antigen response
@ bone marrow
immature B cells
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
mature B cells
have IgM and IgD specific for same antigen
will respond to antigen
mature B cell differentiation
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
plasma cells
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
B/T cell interaction
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
B cell antigen presentation
- protein antigen bound by surface antibody
- receptor mediated endocytosis
- process then expressed on class II MHC
- T cell releases cytokines
- B cell activated
- antibody producing plasma cell
nonprotein antigens CANNOT be used so no lipids or nucleic acids
B cell antibody outcomes
- neutralization of microbes/toxins
- opsonization and phagocytosis of microbes
- antibody dependent cellular cytotoxicity via NK cells
- phagocytosis of microbes opsonized with complement fragments
- inflammation
- lysis of microbes
4-6 via complement activation
TD antigens
thymus dependent
protein antigens are TD bc need T-helper cells
-high affinity antibodies, long lived plasma cells
TI Antigens
general
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
TI-1 antigens
bind non immunoglobulin receptors to promote polyclonal expansion
i.e. LPS acts as B cell mitogen
TI-2 Antigens
bind thru B cell surface immunoglobulin aka only activate antigen-specific B cells
i.e. polysaccharide antigens with repeated epitopes
transduction
signalling thru Ig-alpha and beta
same as CD3 with T cells
Ig structure
2 heavy chains + 2 kappa OR lambda light chains
shared constant regions but differing variable regions
Ig Genes
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
gene segments-variable region
variable region of heavy = VDJ segments for antigen binding
variable region of light = VJ segments for bindign
molecular diversity
-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
gene rearrangment
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)
gene rearrangement sequence
- heavy chains random D and J segments brought together and intervening DNA deleted
- V gene randomlly selected and added to 5’ end of DJ segement = VDJ
- intro separates VDJ from C region gene Cu and CS so that they remain in primary RNA transcript
- process of primary RNA so splice out introns, remove CS, add poly A tail
- mRNA > cytoplasmic u-heavy chain of pre B cells
allelic exclusion
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..
co-expression of IgM and IgD
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
antibody forms
membrane or secreted
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
isotype switching
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
affinity maturation
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
