Specific antibody production by V(H)-gene replacement.

V(H)-gene replacement is a recombination event in which a pre-existing immunoglobulin heavy chain gene can be altered by the replacement of the rearranged V(H) gene segment with another V(H) gene segment. Although this event has been demonstrated in various model systems, its role in generating antibody diversity is still unsettled. We have used a genetically modified mouse strain, QM, with a quasi monoclonal primary B cell repertoire specific for NP to determine whether V(H) gene replacement can generate a new antigen specificity. Hybridomas generated from QM splenocytes after immunization with different antigens, gave rise to antibodies with specificity to the immunizing antigen or with new specificities. We found V(H)-gene replacement was used to change the original heavy chain gene rearrangement specific for NP into a heavy chain gene encoding the new antigen specificity. V(H)-gene replacement intermediates were detected both before and after the immunization, suggesting that the event was selective rather than instructive. These results demonstrate that V(H)-gene replacement can generate a new antibody heavy chain gene with a different functional and selectable antigen specificity.

Platelet alpha-2 adrenoceptors and the menstrual cycle.

To clarify further the suggested influence of menstrual cycle phase on platelet alpha 2-adrenoceptors, we carried out cross-sectional studies in 77 subjects in a clinical trial of weight control strategies. Blood samples were drawn at baseline and after 6 weeks of diet, behavior modification, and exercise, a program that resulted in a mean weight loss of 4.5 kg. For the analyses, 42 premenopausal women were divided into four groups according to the week of menstrual cycle at the time of blood sampling. At baseline, there was no significant difference in mean platelet alpha 2-adrenoceptor numbers among the four groups. At week 6 accompanying the weight loss, there was a significant increase in the platelet alpha 2-adrenoceptor number for all groups. Despite the fact that the women were at a different phase of the menstrual cycle than at baseline, there was again no significant difference in mean platelet alpha 2-adrenoceptor number. Mean baseline platelet alpha 2-adrenoceptor number in the premenopausal women (113.7 +/- 5.5 fmol/mg protein) did not differ from values in 12 postmenopausal women (113.7 +/- 12.0 fmol/mg protein), four women with hysterectomies (105.9 +/- 8.9 fmol/mg protein), or 19 men (101.8 +/- 6.2 fmol/mg protein). Numbers at 6 weeks also did not differ. We conclude that the menstrual cycle has minimal effects on platelet alpha 2-adrenoceptor number and should not confound clinical studies of platelet alpha 2-adrenoceptors.