DEFECTIVE B-CELL DEVELOPMENT IN SNELL DWARF (DW DW) MICE CAN BE CORRECTED BY THYROXINE TREATMENT/

Snell dwarf (dw/dw) mice are deficient in anterior pituitary hormones due to a mutation in the gene encoding the Pit-1 transcription factor, Bone marrow B cell development is also suppressed in the mice, provid ing circumstantial evidence that one or more anterior pituitary-derive d products, or factors induced by them, are required for normal B lymp hopoiesis. However, concluding that this is the case is dependent on s howing that hormonal treatment of dwarf mice reverses their B cell def ects, dw/dw mice were treated with growth hormone (GH), insulin-like g rowth factor-I (IGF-l), or thyroxine in an attempt to restore bone mar row B lymphopoiesis, GH and IGF-I increased the number of B lineage ce lls in the bone marrow and spleen but did not restore the frequency of bone marrow pre-B cells to normal, However, bone marrow cellularity i n thyroxine-treated dw/dw mice was comparable to that in control anima ls, and both the frequency and absolute number of B lineage cells had increased to normal or even above normal, Taken together, these data i ndicate that endocrine factors, especially those regulated by the hypo thalamic-pituitary-thyroid axis, are potent B lymphopoietic factors.