B-Cell Maturation, Activation, and Differentiation

B Cell Receptor

B-cell Receptor

B-cell Receptor & Co- receptors

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

Antigen independent phase of B- cell development

Order 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 Paternal Maternal Allelic Exclusion

Order 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- cell development Bone-marrow stromal cells are required for maturation of pro- B cells into precursor B cells. SCID

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

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

Antigen independent phase of B- cell development transitional B-cell populations, Conventional B2 cells MZ Bcells ( highCD21)

Antigen dependent phase of B- cell 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 proliferating B cells form at the These B cells differentiate into plasma cells secreting.  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 IgM and IgG 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 Cells Are a Self-Renewing B-Cell Subset 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 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 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 suppression Certain vaccines (e.g., those for measles and mumps) are not administered to infants before the age of 1 year ?