B lymphocyte lineage cells in newborn and very young NZB mice: evidence for regulatory disorders affecting B cell formation.
As adults, NZB mice have a severe deficiency of identifiable precursors of B lymphocytes, but this is preceded by a time when B cells and their immediate precursors are present in bone marrow in elevated numbers. Our present studies indicate that the final stages of B cell formation may be proceeding at a greater than normal rate at 4 wk of age. At this time, large numbers of sIg- B cell precursors can be identified in NZB but not in normal CBA/H or DBA/2 marrow that can respond to mitogens in semisolid agar cultures without preculture. Colony formation by these precursors was dependent on the presence of Sephadex G-10-adherent cells in the suspensions. In this respect, 4-wk-old NZB marrow was similar to spleen and liver of normal CBA/H newborn mice. Mixing experiments suggested that hyperactive regulatory cells present in young NZB marrow may promote functional maturation of normal pre-B cells from CBA/H or DBA/2 mice. In addition, potent substances present in the serum of young but not older NZB mice produced the same effect. Factor-mediated enhancement of clonal proliferation by sIg- precursors was not dependent on adherent cells and required more than brief exposure of the cells to young NZB serum. These are all indications that abnormalities of B lineage differentiation in young NZB marrow may be attributable to microenvironmental elements. Congeneic, B cell-deficient NZB.xid mice, however, lacked hyperactive regulatory cell function and serum factors that characterize NZB mice of this age. A study was also made of B cell precursors in newborn spleen and liver of NZB mice, and abnormal shifts of populations of B lineage cells were already present by that time. These observations support previous contentions that humoral immunity is precocious and abnormally regulated in NZB mice.
D000375:Aging; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D001853:Bone Marrow / Q000473:pathology; D002454:Cell Differentiation; D002478:Cells, Cultured; D006133:Growth Substances / Q000502:physiology; D015847:Interleukin-4; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008814:Mice, Inbred NZB / Q000276:immunology*; D009154:Mutation; D011947:Receptors, Antigen, B-Cell / Q000032:analysis; D013234:Stem Cells / Q000276:immunology / Q000473:pathology
D006133:Growth Substances; D011947:Receptors, Antigen, B-Cell; D015847:Interleukin-4