Chapter 10 BCell Development Dr Capers IMMUNOLOGY Development

Chapter 10 B-Cell Development Dr. Capers IMMUNOLOGY

Development of B cells In many vertebrates, including humans and mice, B cells generate in bone marrow Antigen-independent phase Ig-gene rearrangement to create antigen-specificity In the fetus, this happens in the liver Immature B cell bearing Ig. M on membrane leaves bone marrow Matures to express both Ig. M and Ig. D with single antigen specificity NAÏVE B cells – have not encountered antigen Encounter antigen in secondary lymphoid tissue Differentiate into plasma cells and memory cells Class switching

B cell development starts in bone marrow and completes in periphery

B cell development Hematopoietic Stem Cell can develop into Common Lymphoid Progenitor cell (CLP) CLP can develop into Pro-B cell develops into Pre-B cell develops into immature B cell Immature B cells leave bone marrow Travels to spleen where it matures Mature B cell leaves spleen ○ Expressing high Ig. D and some Ig. M on surface Migrate to lymphoid follicles ○ When B cell comes into contact with antigen in germinal center: - Proliferation, hypermutation, class switching

Bone marrow Pro-B cell → precursor B cell Stromal cell in bone marrow secrete IL-7 that help development into immature B cells

Pro-B Cell ○ Heavy chain rearrangement Pre-B cell ○ Light chain rearrangement Immature B cell ○ Is now committed to antigenic specificity and produces Ig. M ○ B cell not fully functional, must first express both Ig. M AND Ig. D on membrane

In mice, 90% of B cells produced everyday die without ever leaving bone marrow ○ Negative selection due to cells that express auto-antibodies against self antigen in the marrow