B-Cell Maturation,B-Cell Maturation,Activation, andActivation, andDifferentiationDifferentiation

B Cell ReceptorB Cell Receptor

B-cell ReceptorB-cell Receptor

B-cell Receptor & Co- receptorsB-cell Receptor & Co- receptors

Antigen independentindependent phase of B-cell development

Antigen dependentdependent phase of B-cell development.

B-Cell MaturationB-Cell Maturation,,

Antigen independent phase of B-Antigen independent phase of B-cell developmentcell development

Antigen independent phase of B-Antigen independent phase of B-cell developmentcell development

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)

Antigen dependent phase of B-Antigen dependent phase of B-cell developmentcell development

TH Cells Play Essential Roles in Most B-Cell Responses

Hyper IgM Syndrome

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..

proliferation and class switchingproliferation and class switching

The eosinophils and megakaryocytes provide the

longlivedplasma cell

Primary and Secondary ResponsesPrimary and Secondary Responses

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.

Negative regulation B cell

• CD32

• CD22

• B10 Bcell

Antibody mediated suppressionAntibody mediated suppression

Certain vaccines (e.g., those for measles and Certain vaccines (e.g., those for measles and mumps) are not administered to infants before mumps) are not administered to infants before

the age of 1 yearthe age of 1 year? ?