Induction of isotype switching and Ig production by CD5+ and CD10+ human fetal B cells.
In the present study the capacity of early fetal B cells to produce Ig was investigated. It is shown that B cells from fetal liver, spleen, and bone marrow (BM) can be induced to produce IgM, IgG, IgG4, and IgE, but not IgA, in response to IL-4 in the presence of anti-CD40 mAb or cloned CD4+ T cells. Even splenic B cells from a human fetus of only 12 wk of gestation produced these Ig isotypes. IFN-alpha, IFN-gamma, and transforming growth factor-beta inhibited IL-4-induced IgE production in fetal B cells, as described for mature B cells. The majority of B cells in fetal spleen expressed CD5 and CD10 and greater than 99% of B cells in fetal BM were CD10+. Highly purified CD10+, CD19+ immature B cells and CD5+, CD19+ B cells could be induced to produce Ig, including IgG4 and IgE, in similar amounts as unseparated CD19+ B cells. Virtually all CD19+ cells still expressed CD10 after 12 days of culture. However, the IgE-producing cells at the end of the culture period were found in the CD19-,CD10- cell population, suggesting differentiation of CD19+,CD10+ B cells into CD19-,CD10- plasma cells. Pre-B cells are characterized by their lack of expression of surface IgM (sIgM). Only 30 to 40% of BM B cells expressed sIgM. However, in contrast to sIgM+,CD10+,CD19+ immature B cells, sorted sIgM-,CD10+,CD19+ pre-B cells failed to differentiate into Ig-secreting cells under the present culture conditions. Addition of IL-6 to these cultures was ineffective. Taken together, these results indicate that fetal CD5+ and CD10+ B cells are mature in their capacity to be induced to Ig isotype switching in vitro as soon as they express sIgM.
Punnonen
J
J
DNAX Research Institute, Palo Alto, CA 94304-1104.
Aversa
G G
GG
Vandekerckhove
B
B
Roncarolo
M G
MG
de Vries
J E
JE
D000917:Antibody Formation; D015703:Antigens, CD / Q000032:analysis / Q000502:physiology; D018941:Antigens, CD19; D000943:Antigens, Differentiation / Q000032:analysis; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis / Q000502:physiology; D000951:Antigens, Neoplasm / Q000032:analysis; D016175:B-Lymphocyte Subsets / Q000502:physiology*; D001853:Bone Marrow / Q000196:embryology; D019013:CD40 Antigens; D018956:CD5 Antigens; D005333:Fetus; D005434:Flow Cytometry; D015322:Gene Rearrangement, B-Lymphocyte; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000235:genetics; D007372:Interferons / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008099:Liver / Q000196:embryology; D015260:Neprilysin; D013154:Spleen / Q000196:embryology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D015703:Antigens, CD; D018941:Antigens, CD19; D000943:Antigens, Differentiation; D000944:Antigens, Differentiation, B-Lymphocyte; D000951:Antigens, Neoplasm; D019013:CD40 Antigens; D018956:CD5 Antigens; D007132:Immunoglobulin Isotypes; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007073:Immunoglobulin E; D007372:Interferons; D015260:Neprilysin