Development of B lymphocytes Parham, Chapter 4 H. HogenEsch, 2004

B cell development Fig. 4.2 H. HogenEsch, 2004

IgM IgG IgE IgA antigen-independent pre-B cell immature B cell stem cell ( m chain +) (IgM +) (IgM + , IgD +) antigen-dependent IgM isotype switching IgG IgE IgA H. HogenEsch, 2004

Pre-B cell pre-B cell receptor = m + surrogate light chain H. HogenEsch, 2004

B cell development in bone marrow H. HogenEsch, 2004 Bone marrow stromal cells

Ig gene rearrangements – allelic exclusion H. HogenEsch, 2004 Fig. 4.6

Sequential L chain gene segment rearrangements H. HogenEsch, 2004

Immunoglobulin gene expression during B cell development H. HogenEsch, 2004

Selection of immature B cells Fig. 4.13 H. HogenEsch, 2004

Receptor editing H. HogenEsch, 2004

B-1 cells vs. B-2 cells H. HogenEsch, 2004

B-1 cells vs. B-2 cells (cont’d) H. HogenEsch, 2004

X-linked agammaglobulinemia Recurrent infections of extracellular bacteria Recessive, X-linked Defect in Bruton’s tyrosine kinase Nearly complete absence of circulating immunoglobulins Reduced number of pre-B cells in bone marrow, lack of mature B cells Normal thymus and normal number of T cells H. HogenEsch, 2004

Circulation of naïve B cells Fig. 4.15 H. HogenEsch, 2004

Further development of mature B cells H. HogenEsch, 2004

Effect of specific antigen on B cell migration and differentiation Fig. 4.16 H. HogenEsch, 2004

Histology of the lymph node cortex M = mantle zone GC = germinal center D = dark zone L = light zone H. HogenEsch, 2004

B cell life cycle days - weeks Naïve B cell apoptosis Ag 5 days IgM paracortex medulla months bone marrow IgG germinal center isotype switching memory B cell H. HogenEsch, 2004

B cell tumors H. HogenEsch, 2004

Burkitt’s lymphoma H. HogenEsch, 2004