Further, we could also distinguish the individual stages based on the sequential steps of initiation, propagation, and integration of intracellular signal transduction cascades. The step of signal initiation is considered to represent the early events that occur upon receptor engagement, and this early upstream process regulates the downstream targets both qualitatively and quantitatively. A mathematical model helps to define key regulators of system homeostasis and Lyn activation Although we could successfully prove the role of p38 in regulation of Lyn by acting on SHP 1, it did not address the issue of cell type specificity in determining cell fate decisions. It has been reported that levels of phospho Lyn and other intermediates are significantly higher in immature B cell compared to the mature coun To take into account the particular nature of the negative regulator as discussed above we assumed, terpart cells.

We also observed this feature in our present study, when compared with our earlier studies involving mature B cells. Since we had sufficient information on both mature and immature counterparts regarding their basal status and the way they respond to the antigen we sought to build a mathematical model representing the fundamental differences in both of these cell types, in terms of the initiation of BCR signaling. For this we built a model based on a system of ordin ary differential equations to analyze Lyn activation and its down stream effect on Syk activation.

Here, while the extent of BCR dependent Lyn activation by phos phorylation was treated as a measure of the strength of initial signal generated, the magnitude of Syk activation would then define the efficiency of its transduction to the downstream intermediates. The aim here was to identify the key parameter that might lead to weak activation of BCR dependent signals in immature B Here a is the forcing term representing the strength of the stimulation. At ground state a 0. In unstimulated cells, there is an equilibrium main tained between Brefeldin_A the active and inactive state of the sig naling molecules such as Lyn and Syk. However, it must be emphasized here that there are indeed multiple states of signaling intermediates present in the real system due to multiple phosphorylation sites. But our focus here was to analyze the balance between the active and inactive forms of the species and their differ ential response to varying basal activity.

Therefore in the considered scenario, mathematically, at ground state i. e,a 0, we define the basal value of active Lyn denoted by Lp as the value where, cells, as opposed to that in mature B cells. More specifi cally, we wanted to determine whether the higher levels of basally active Lyn in immature B cells could account for this difference. In our model, we also incorporated the role of SHP 1 as a negative regulator of BCR signal ing.