B-Cell Maturation, Activation, and Differentiation.
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Transcript of B-Cell Maturation, Activation, and Differentiation.
Antigen independentindependent phase of B-cell development
Antigen dependentdependent phase of B-cell development.
B-Cell MaturationB-Cell Maturation,,
Order of Ig Gene ExpressionOrder of Ig Gene Expression
+
-
Heavy chain gene
VDJ recombination
Productive rearrangement ?
Yes
No
Transcribe/translate
1st
2nd
or
Apoptosis
Progenitor B cell
Pre B cell
() Heavy chain
PaternalMaternal
Allelic Allelic ExclusionExclusion
Order of Ig Gene ExpressionOrder of Ig Gene Expression
+
-
Light chain gene
VJ recombination
Productive rearrangement ?
Yes
No
Transcribe/translate
Light chain
4 th
Apoptosis
1st -
2nd -
3rd -
4th -
or
Pre B cell
Mature B cell
+
Antigen independent phase of B-Antigen independent phase of B-cell developmentcell development
Bone-marrow stromal cells are required for maturationof pro- B cells into precursor B cells.
SCID
Antigen independent phase of B-Antigen independent phase of B-cell developmentcell development
The Pre–B-Cell ReceptorPre–B-Cell Receptor Is Essential for B-Cell Development
?
Bruton Agamaglobolinemia
Antigen independent phase of Antigen independent phase of B-cell developmentB-cell development
IgM -bearing immature B cellimmature B cell: antigen induces death or unresponsiveness (anergy) or receptor editing
Autoimmunity≈ SLE
Antigen independent phase of B-Antigen independent phase of B-cell developmentcell development
tran
sitio
nal B
-cel
l pop
ulat
ions
,
Conventional B2 cells
MZ Bcells ( highCD21)
Once antigen-mediated B-cell activation takes place, small foci of Once antigen-mediated B-cell activation takes place, small foci of proliferating B cells form at the proliferating B cells form at the edges of the T-cell–rich zone. These B These B cells differentiate into plasma cells secreting cells differentiate into plasma cells secreting IgM and IgG isotypes..
Thymus-Dependent and Thymus-Thymus-Dependent and Thymus-Independent Antigen Have Different Independent Antigen Have Different
Requirements for ResponseRequirements for Response
B-1 B-1 B Cells Cells Are a Self-Renewing B-Cell Subset Are a Self-Renewing B-Cell Subset
• In humans and mice, B-1 B cells compose about 5% of the total B-cell population.
• They appear during fetal life, express surface IgM but little or no IgD, and are marked by the display of CD5
• The B-1 population responds poorly to protein antigens but much better to carbohydrate ones
• This population undergoes much less somatic hypermutation and class switching than the B-2 set of B cells does Consequently, the antibodies produced by a high proportion of B-1 cells are of rather low affinity.
• Natural Antibody• IgM and IgG antibodies induced by Tl-2 antigens are likely to be an
important part of the humoral immune response in many bacterial infections,
MZ B Cells MZ B Cells Are a Self-Renewing B-Cell Subset Are a Self-Renewing B-Cell Subset
• MZ B cells bear unusually high levels of CD21 (CR2)• MZ B cells are particularly important in the host
protection against pathogens bearing TI-2 antigens.• MZ B cells are specialized to respond to blood-borne
antigens that enter the immune system via the splenic MZ.
• in rodents, B cells with the characteristics of MZ cells are restricted to the MZs of the spleen, whereas in primates they can be found in other peripheral lymphoid tissues such as the tonsils.