Lecture 6 - B cells and antibodies

– Antibody - soluble version of BCR

– Structure
2
– Immunoglobulin fold domains
1
– Specificity, effector function, flexibility
– Antigen binding site, hinge region
– Classes / Isotypes
– Types, how and why they are distinguished
– Generation of antibody diversity
– Variation, diversity, junctional gene segments (VDJ)
– Variations in variable domains
– Variations in CDR3
– Variations in heavy chains
Variation in variable Variation in heavy Variation in light
domains chains chains
Variable gene VDJ rearrangement No diversity gene
segments segments
CDR3 - diversity gene 1. D —> J joining 1. K chain rearranges
segments and first
junctional gene
segments, and
variations in the
junctions between ??
VDJ
(CDR3 is the most 2. V —> DJ joining ;; all 2. If fail, lambda chain
variable CDR) genomic DNA in rearrangements
between is lost
(Both by somatic Allelic exclusion - if a (Uses recombinases
rearrangement) functional heavy chain RAG1 and RAG2,
is produced on one involve…)
allele, the other allele
is prevented from
rearrangement

Process
. Antigen binds to B cells and gets internalised in the B cell
. Free antigens (same kind) are loaded onto MHC class II and presented
to T cells. T cells activates that B cells to proliferate. Proliferating B
cells acquire mutations. B cells w/ BCRs of a stronger affinity to that
 .

antigen can interact more strongly with follicular dendritic cells (FDCs)
bearing that antigen. They shuttle between T follicular helper cells and
FDCs and increase in number due to survival signals

Isotype switching
– Initially produce IgM and IgD isotopes
2
– By alternative splicing and are co-expressed
– Each B cell can then change the constant region to IgG, IgA or IgE