BCell Maturation Activation and Differentiation B Cell Receptor

B-Cell Maturation, Activation, and Differentiation

B Cell Receptor

B-cell Receptor

B-cell Receptor & Co- receptors

B-Cell Maturation, q Antigen independent phase of B-cell development q Antigen dependent phase of B-cell development.

Antigen independent phase of Bcell development

Order of Ig Gene Expression Progenitor B cell 1 st Heavy chain gene + 2 nd VDJ recombination No Productive rearrangement ? - Apoptosis Yes Transcribe/translate ( ) Heavy chain Maternal or Pre B cell Paternal Allelic Exclusion

Order of Ig Gene Expression or Pre B cell Light chain gene + 4 th 1 st - VJ recombination 2 nd - 3 rd - No Productive rearrangement ? 4 th - - Apoptosis Yes Transcribe/translate Light chain + Mature B cell

Antigen independent phase of Bcell development üBone-marrow stromal cells are required for maturation of pro- B cells into precursor B cells. SCID

Antigen independent phase of Bcell development ? üThe Pre–B-Cell Receptor Is Essential for B-Cell Development Bruton Agamaglobolinemia

Antigen independent phase of B-cell development ü Ig. M -bearing immature B cell: cell antigen induces death or unresponsiveness (anergy) or receptor editing Autoimmunity≈ SLE

Conventional B 2 cells tra ns itio na l. B -ce ll p op ula tio ns , Antigen independent phase of Bcell development MZ Bcells ( high. CD 21)

Antigen dependent phase of Bcell development

TH Cells Play Essential Roles in Most B-Cell Responses Hyper Ig. M Syndrome

q. Once antigen-mediated B-cell activation takes place, small foci of proliferating B cells form at the edges of the T-cell–rich zone. These B cells differentiate into plasma cells secreting Ig. M and Ig. G isotypes. .

proliferation and class switching

The eosinophils and megakaryocytes provide the longlived plasma cell

Primary and Secondary Responses

Thymus-Dependent and Thymus. Independent Antigen Have Different Requirements for Response

B-1 B Cells Are a Self-Renewing B-Cell Subset • In humans and mice, B-1 B cells compose about 5% of the total Bcell population. • They appear during fetal life, express surface Ig. M but little or no Ig. D, and are marked by the display of CD 5 • 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 • Ig. M and Ig. G 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 Are a Self-Renewing B-Cell Subset • MZ B cells bear unusually high levels of CD 21 (CR 2) • 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 • CD 32 • CD 22 • B 10 Bcell

Antibody mediated suppression Certain vaccines (e. g. , those for measles and mumps) are not administered to infants before the age of 1 year ?