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Phenotypic and functional characteristics of human newborns' B lymphocytes
A Durandy1, L Thuillier, M Forveille
1INSERM U 132, Hôpital des Enfants Malades, Paris, France.
Insights
Human newborns
Area of Science:
- Immunology
- Neonatal Immunology
- B cell Biology
Background:
- Human newborns' B lymphocytes exhibit unique characteristics, including poor differentiation into immunoglobulin-producing cells and expression of CD5 and CD1c membrane proteins.
- These B cells express activation antigens like 4F2 and IL-2R, associated with CD23 and Bac-1, on both CD5(+) and CD5(-) populations.
Purpose of the Study:
- To further characterize the unique features of human newborns' B cells.
- To investigate the activation status and proliferative capacity of neonatal B cells.
Main Methods:
- Flow cytometry analysis of B cell surface markers (CD5, CD1c, 4F2, IL-2R, CD23, Bac-1, IgD).
- Assessment of cell cycle phase through size, RNA, and DNA content analysis.
- Stimulation of B cell proliferation using recombinant interleukins (rIL-2, rIL-4), B cell growth factor, and Staphylococcus aureus protein A.
Main Results:
- Newborn B cells express activation antigens (4F2, IL-2R) but not other markers, and retain surface IgD, indicating a G0/G1 cell cycle phase.
- Proliferation of these B cells can be induced by various growth factors and stimuli.
- The study highlights potential complexities in B cell subsets or maturation stages in newborns.
Conclusions:
- Newborn B cells possess distinct activation profiles and proliferative potential compared to adults.
- The findings suggest that partially activated B cells may produce natural polyspecific autoantibodies of the IgM isotype in newborns.
- Further research is needed to clarify the distinct subsets or maturation pathways of CD5(+) and CD5(-) B cells in neonatal life.
Abstract:
It has been demonstrated two major facts concerning human newborns' B lymphocytes: 1) they differentiate poorly into Ig-producing cells and 2) they express CD5 and CD1c membrane proteins. We have further analyzed human newborns' B cell characteristics and found that approximately half of them express activation Ag, i.e., 4F2 and IL-2R, both associated in significant proportions with CD23 and Bac-1. These membrane Ag were found both on CD5(+) and CD5(-) B cells. Newborns' B cells do not exhibit other activation markers because they express surface IgD, and because their size, RNA, and DNA contents do not differ from those of adults' B cells, indicating that they are in the G0/G1 cell cycle phase. Newborns' B cell proliferation can be induced by rIL-2, rIL-4, low m.w. B cell growth factor, and by Staphylococcus aureus protein A. It is presently difficult to build a hypothesis accounting for all the specific findings made on newborns' B cells. It is not known for instance whether CD5(+) and (-) B cells belong to distinct subsets as suggested by the fluorescence intensity curve obtained with an anti-CD5 antibody or to distinct stages in a unique pattern of B cell maturation during fetal and newborn life. This may indicate that partially activated B cells actually produce natural polyspecific autoantibodies of the IgM isotype found in newborns' human serum.