Snmek 1

1
B lymphocytes and antibody production
2
B LYMPHOCYTES
are responsible for the generation of specific
humoral immunity (production of antibodies) -
are under the regulation of T cells
DIFFERENTIATION (antigen independent)
in bone marrow changes in cell membrane
molecules and in morphology precursor ? pre
B ? mature B ? plasma cell rearrangement
of genetic information coding receptors for
antigen (BcR) BcR complex membrane expression
3
RECEPTORS FOR ANTIGEN ON B CELL (BcR)
same genetic rules as for TcR (V, D, J
recombination, C) limited selection for
self specific recognition of unprocessed,
native antigens (spatial conformation) somatic
mutation changes of BcR in the presence of
antigen (affinity maturation)
4
ORGANISATION OF IgH LOCUS
NUCLEOTIDE SEQUENCES BETWEEN GENE
SEGMENTS (12-23 RULE )
12 bp
CACAGTG
ACAAAAACC
Vk
GTGTCAC
TGTTTTTGG
Jk
23 bp
5
REARRANGEMENT OF V-J GENE SEGMENTS (LIGHT
CHAIN)
J1
V2
V4
V1
V2
V3
J2
J3
9
9
RAG -1,2
RAG -1,2
12
23
7
7
V2
V1
J2
J3
6
DIFFERENTIATION OF B CELLS (antigen
independent)
HLA II
HLA II
(CD 34 )
CD 19
rearrangement
TdT
CD 10
cCD 79a
c?
CD 19
HLA II
CD 19
MATURE B CELL
Y
CD 79a
BcR
CD 79b
7
DIFFERENTIATION B CELLS (antigen driven)
takes place in secondary organs of immune
system
lymph node, spleen, mucosa the site of B cell-
antigen encounters proliferation of B cells,
terminal differentiation germinal center primary
production of antibodies immunoglobuline
molecules are soluble forms of BcR
8
DIFFERENTIATION INTO PLASMA CELL
antigenic stimulus
TH2 help
B cell
somatic mutation
izotypic switching
Y
Y
Y
Y
immunoglobulins solubile forms BcR
9
B- CELLS - RECOGNITION OF ANTIGEN (BcR)
C3d
Ag
CD 23
sIgM
H
H
L
L
CD 19
CD81
CD79 a,b
TAPA-1
?
?
?
?
ITAM
ITAM
ITAM
ITAM
ITAM
Lyn
B - cell
kinases
10
SECONDARY LYMPHATIC FOLICLE
B-cells
marginal zone
plasma cells
mantle zone
germinal centre
mutation og genes for Ig affinity maturation
memory B-cells
11
T- B CELLS INTERACTIONS
intimate cell-cell contact B cells are able to
process and present antigens to T
cells cognitive interactions through
BcR costimulatory interactions cytokines
regulated
12
T CELLS, B CELLS INTERACTIONS
IL - 4
FceR II.
CD 21
TH2
CD40L
CD40
B cell
plasma cell
TCR
Y
Y
costimulation
Y
Y
Y
Y
Y
Y
Y
Y
IL - 13
specific antibidies
13
ISOTYPIC SWITCHING
primary antibodies are IgM isotype
(C? is the nearest to VDJ) other
isotypes are generated after additional gene
rearrangement regulated by T cell system
cytokines IL-4
T-B cell contact CD40L ? CD40
development of germinal center
14
Isotypic switching
S
S
S
C? 1
S
S
C? ?
C?1
C? 3
C? 1
C? ?
S
C? 2
S
C?1
S
C? 3
S
C?
C? 4
Cm
C? 2
C?
S
S
S
C? 4
Cm
S
S
S
V
D
J
Ce
Ca2
C?
C? 2
promotor
enhancer
V
D
J
15
? Krejsek, 2004